ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.2125G>T (p.Ala709Ser)

gnomAD frequency: 0.00003  dbSNP: rs201468881
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001184689 SCV001350725 likely benign Familial thoracic aortic aneurysm and aortic dissection 2020-01-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001194120 SCV001363408 uncertain significance not specified 2019-03-25 criteria provided, single submitter clinical testing Variant summary: COL3A1 c.2125G>T (p.Ala709Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 282470 control chromosomes, predominantly at a frequency of 0.00045 within the East Asian subpopulation in the gnomAD database. The observed frequency in the East Asian subpopulation is 360-folds higher than the estimated maximum expected allele frequency for a pathogenic COL3A1 variant of 1.3e-06. To our knowledge, no occurrence of c.2125G>T in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS - possibly benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV001369968 SCV001566427 uncertain significance Ehlers-Danlos syndrome, type 4 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 709 of the COL3A1 protein (p.Ala709Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs201468881, ExAC 0.06%). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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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