ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.1873C>T (p.Pro625Ser)

gnomAD frequency: 0.00002  dbSNP: rs747419192
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001049697 SCV001213764 uncertain significance Ehlers-Danlos syndrome, type 4 2023-11-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 625 of the COL3A1 protein (p.Pro625Ser). This variant is present in population databases (rs747419192, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 846400). 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 with a negative predictive value of 95%. 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.
GeneDx RCV001824407 SCV002074038 uncertain significance not provided 2022-01-31 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain at the X 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 X position is not a common mechanism of disease (HGMD); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 846400)

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