ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.119C>T (p.Ala40Val) (rs201380807)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766806 SCV000233321 uncertain significance not provided 2018-08-27 criteria provided, single submitter clinical testing A40V has been reported in one individual with non-syndromic TAAD (Sakai et al., 2012). The A40V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nevertheless, the A40V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, missense mutations in nearby residues have not been reported in the Human Gene Mutation Database (Stenson et al., 2014), and the A40V variant does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL3A1gene, where the majority of missense mutations occur (Symoens et al., 2012).Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000355476 SCV000425495 likely benign Ehlers-Danlos syndrome, type 4 2016-06-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000181046 SCV000538717 uncertain significance not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1 paper, no segs, ExAC: 3/8646 East Asian chromosomes
Center for Human Genetics, Inc RCV000659410 SCV000781221 uncertain significance Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000355476 SCV000958207 uncertain significance Ehlers-Danlos syndrome, type 4 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 40 of the COL3A1 protein (p.Ala40Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs201380807, ExAC 0.03%). This variant has been observed in an individual affected with aortic aneurysm and/or dissection (PMID: 22001912). ClinVar contains an entry for this variant (Variation ID: 199690). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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