ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.2273A>G (p.Asp758Gly)

dbSNP: rs2153503070
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001769294 SCV002003449 uncertain significance not provided 2020-10-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (Stenson et al., 2014)
Labcorp Genetics (formerly Invitae), Labcorp RCV001868587 SCV002212143 uncertain significance Ehlers-Danlos syndrome, type 4 2021-09-04 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 758 of the COL3A1 protein (p.Asp758Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 not expected to disrupt COL3A1 protein function.

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