ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.1972G>A (p.Glu658Lys) (rs189846410)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000780195 SCV000917255 uncertain significance not specified 2018-10-29 criteria provided, single submitter clinical testing Variant summary: COL3A1 c.1972G>A (p.Glu658Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 245454 control chromosomes (gnomAD). 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.1972G>A in individuals affected with Aortopathy 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.
Invitae RCV000548065 SCV000631637 uncertain significance Ehlers-Danlos syndrome, type 4 2017-06-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 658 of the COL3A1 protein (p.Glu658Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs189846410, ExAC 0.01%). This variant has not been reported in the literature in individuals with a COL3A1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Unknown"; Align-GVGD: "Class C55"). In summary, this variant has uncertain impact on COL3A1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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