ClinVar Miner

Submissions for variant NM_001278074.1(COL5A1):c.514G>A (p.Val172Ile) (rs150147262)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198204 SCV000249774 uncertain significance not provided 2016-01-11 criteria provided, single submitter clinical testing The V172I variant of uncertain significance in the COL5A1 gene has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or in the 1000 Genomes Project. Although this substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species, it is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, in silico analysis predicts this variant likely does not alter the protein structure/function. Furthermore, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with EDS (Stenson et al., 2014), indicating that this region of the gene is not known to harbor disease-causing variants. Moreover, the V172I variant does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL5A1 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Ambry Genetics RCV000620897 SCV000738646 likely benign Cardiovascular phenotype 2017-06-29 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Invitae RCV001088420 SCV001009031 likely benign Ehlers-Danlos syndrome, classic type 2019-12-31 criteria provided, single submitter clinical testing

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