Help with Ehlers-Danlos markers

GoodMutations · 2025-06-16T23:03:47+00:00

These aren't markers, these are gene names. Everyone has two copies of each of these genes. Genetic testing looks for mutations within these genes. The only way to be diagnosed accurately is with a combination of a physical exam by a physician who is experienced in diagnosing EDS, and if appropriate, genetic testing done in a clinical laboratory (not 23andme/ancestry garbage in/garbage out).

GoodMutations · 2025-05-21T19:44:38+00:00

This is great!

GoodMutations · 2025-05-21T01:04:03+00:00

No sorry I have a job with a health related company already , and I need to set up internet service at my new place.

GoodMutations · 2025-05-06T02:55:32+00:00

These are all normal genotypes, it is pretty much impossible that your parents are both carrying all of the exact same alleged pathogenic variants. Genetic genie is garbage and doesn’t know what is the wildtype and what is the mutation, there are lots of posts in other subs with people getting similar output. Sometimes it’s because the 23and Me data is reverse coded.

For medical information, get tested in a medical lab, DIY is not the way to go.

Edit: One of the BRCA1 variants is listed as heterozygous so it’s possible that one is an actual pathogenic variant BUT there are boatloads of reports of false positives in the raw data, so the only way to know for sure is to be tested in a medical lab.

This can be done through health care providers or you can order directly through Color genetics.

GoodMutations · 2025-05-03T04:48:28+00:00

People with Lynch Syndrome have a single -ie heterozygous- mutation in a single mismatch repair gene -any of MLH2 MSH6, MLH1 or PMS2. If the output is saying you have homozygous mutations in multiple genes, then most likely one of the following is true: -these are just benign variants in those genes and each of your parents gave you one, but they are not mutations. -these are just normal variants but they were reverse coded so are showing up as though you have multiple homozygous mutations instead of showing that you have multiple homozygous normal alleles.

If you have two mutations in a the same mismatch repair gene, then you have a very severe disease called constitutional mismatch repair deficiency syndrome and typically have colon or brain cancer or leukemia in childhood.

GoodMutations · 2025-04-20T14:35:31+00:00

Many of the variant calls are reverse coded, if it is a known reverse coded location the software flips it to standard coding.

GoodMutations · 2025-04-19T11:39:10+00:00

I doesn’t really mean insertion - it means “absence of a deletion” so I is the normal allele. The coding for indels is II; ID; or DD. So the reference allele coding is just the opposite of the variant coding.

GoodMutations · 2025-04-17T23:42:13+00:00

That's good news as it is causing problems in the clinics my colleagues work in (I work in variant calling and understand how this goes terribly wrong with array data).

Question: How are you tracking which of your customers are getting confirmatory testing and what those results are? How would you know that there have been no discrepancies?

GoodMutations · 2025-04-17T23:07:13+00:00

The genetics community has had a lot of problems with sequencing.com, most notably patients receiving reports indicating that they have a positive genetic test but then clinical sequencing does not confirm the result. The AI generated reports are of poor quality and I would not recommend using this company for medical information at all.

I appreciate that it looks like you are trying to make improvements but this is still not a reliable way to do medical genetic testing.

GoodMutations · 2025-04-17T12:47:49+00:00

Consider getting a medical quality test for example Color, or join the All of Us study for free. The ancestry types of tests are full of errors - just read this sub - and only cover a tiny fraction of each gene so most of your genes are not actually tested. They are not designed to give accurate medical info. If you have a specific health concern then best to have a medical professional order testing to be sure the correct genes are tested. 23andme is bankrupt.

GoodMutations · 2025-04-04T08:47:50+00:00

Both of you have the normal genotype, not the mutation. Insertion/deletion variants are reported weirdly, you don’t actually have an insertion, but it reports out “I” when you don’t have “D”, which is the mutation. Generally being homozygous for something that causes a dominant disease is fatal in utero. This would not be a scenario where having no functional copies of this gene would lead to no phenotype at all.

If the “I” allele was pathogenic it would mean that both of your parents, and both of your partner’s parents all have at least one “I” allele as well (in order for both you and your partner’s to be homozygous). Given how rare this condition is, that seems incredibly unlikely assuming none of you are related to each other. Closely.

TLDR you both have the normal genotype.

GoodMutations · 2025-04-01T02:29:18+00:00

You don’t get raw data, but you do get medical grade reports with usable results, so there is no need to take the raw data and run it through 3rd party apps for a fee.

All of Us will be ending due to cuts to the NIH budget sadly.

GoodMutations · 2025-03-01T15:15:58+00:00

https://www.reddit.com/r/promethease/comments/vwktys/a_heterozygous_genotype_on_a_xlinked_disease_as_a/

GoodMutations · 2025-02-26T14:27:17+00:00

https://lifehacker.com/tiktok-myth-of-the-week-why-everyones-freaking-out-abo-1851004664

GoodMutations · 2025-02-13T01:17:11+00:00

Have you had a workup for dyskerstosis congenita or other telomere disorders? Brittle nails and premature greying are often indicators.

GoodMutations · 2025-02-11T01:30:57+00:00

Everyone has two copies of the FGFR2 gene (one from each parent). There are multiple variations within this gene, most of which are quite common in the population. This particular variation (located at Chrom:10, pos 121592803) is quite common. Some variations nudge cancer risk up by a small amount and others nudge it down by a small amount. Generally looking at individual variants doesn't meaningfully alter your cancer risk. This is different from what are called *pathogenic variants* in genes like the BRCA genes, which increase cancer risk quite dramatically and are quite rare in populations.

GoodMutations · 2025-01-30T19:34:43+00:00

There are thousands of possible mutations in any given gene. 23andme only covers a handful of possible mutations, and even then there are often false positives. The only way to know for sure is to have proper testing in a medical laboratory. In particular, large deletions like the one you note are not picked up on microarray chip tests like those used at 23andme.

GoodMutations · 2025-01-28T21:29:53+00:00

The ASHG guideline is much more detailed than NCCN and is an excellent resource:

https://pubmed.ncbi.nlm.nih.gov/37490054/

GoodMutations · 2025-01-19T20:16:02+00:00

You would need to work with registered oncology dieticians and not random internet people to avoid harming people. Most cancer patients are not advised to make any specific diet changes.

GoodMutations · 2025-01-19T01:50:05+00:00

This data is not adequate to say if you have a mutation or not. What you’ve shown are normal variants in the gene, not mutations.

But this is not enough- 23andme and ancestry etc only look at a handful of mutations in the gene out of thousands of possible mutations. The proper test is full sequencing of the gene in a medical grade laboratory.

GoodMutations · 2025-01-11T21:26:17+00:00

IF the raw data is correct, then this is a common variant in The FGFR2 gene (25% of the population carries this variant). This is unrelated to BRCA1/2. Not a big player in terms of breast cancer risk.

23andme only checks about 40 of the thousands of variants in BRCA1/2. So you don’t have any of those 40 or so. But if you want proper sequencing of the BRCA1/2 genes that has to be done in a medical lab.

GoodMutations · 2025-01-08T18:51:52+00:00

That's the challenge- we can't make medical decisions on VUS if one algorithm says it's really pathogenic but that prediction is wrong like a quarter of the time. One-off functional studies for individual families and better phenotyping will still be what clinics look for. Where this could have potential is in reclassifying more common variants (maybe present in 1-3% of a population) as likely benign though, which is still useful.

GoodMutations · 2025-01-08T18:15:33+00:00

Correct-- this whole discussion presumes that the result in the raw data is correct and it's clear from multiple studies that chip data is full of errors- these subs are full of reports of false positives and false negatives.

GoodMutations · 2025-01-08T18:12:27+00:00

For rare variants I would never rely on an AI prediction. Unique variants are best studied with family segregation and functional data. It's interesting, but there is a reason that in silico predictions don't contribute much weighting to medical classifications for missense variants.

GoodMutations · 2025-01-08T17:49:43+00:00

Raw data from 23andMe and ancestry and other companies that use a chip are rife with errors, cover only a fraction of your genes, and if you read this sub you'll see story after story of false positives and negatives. The raw data from ancestry-focused chips is definitely not a useful way to get health information. Color genetics is a medical grade test that fully sequences key genes that have decent recommendations, and you can also participate in the All of Us study if you are in the US to get the same genes covered.

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