ClinVar Miner

Submissions for variant NM_000093.4(COL5A1):c.2588A>T (p.Glu863Val) (rs139788610)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000250443 SCV000320110 uncertain significance Cardiovascular phenotype 2016-04-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
GeneDx RCV000199282 SCV000249903 uncertain significance not specified 2017-03-21 criteria provided, single submitter clinical testing Although the E863V variant has not been published as a pathogenic variant or as a benign variant to our knowledge, it has been previously identified in other unrelated individuals who underwent genetic testing for Marfan/TAAD The E863V variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, while the E863V variant occurs within the triple helical region of the COL5A1 gene, it does not affect a Glycine residue in a Gly-X-Y motif, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). Furthermore, the NHLBI Exome Sequencing Project and the 1000 Genomes Project report E863V was observed in approximately 0.1% of alleles from individuals of European and African background. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV000550293 SCV000631471 likely benign Ehlers-Danlos syndrome, classic type 2017-12-10 criteria provided, single submitter clinical testing

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