ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.343G>T (p.Gly115Cys)

dbSNP: rs964468427
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001997918 SCV002251258 uncertain significance Ehlers-Danlos syndrome, type 4 2021-07-09 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL3A1 protein function. 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. This sequence change replaces glycine with cysteine at codon 115 of the COL3A1 protein (p.Gly115Cys). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002236193 SCV002512026 uncertain significance not specified 2022-04-18 criteria provided, single submitter clinical testing Variant summary: COL3A1 c.343G>T (p.Gly115Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249320 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.343G>T in individuals affected with Ehlers-Danlos Syndrome, Vascular Type and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV003289315 SCV004008129 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-05-08 criteria provided, single submitter clinical testing The p.G115C variant (also known as c.343G>T), located in coding exon 4 of the COL3A1 gene, results from a G to T substitution at nucleotide position 343. The glycine at codon 115 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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