ClinVar Miner

Submissions for variant NM_000093.5(COL5A1):c.5504G>C (p.Cys1835Ser)

dbSNP: rs1060502246
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002230377 SCV000548980 likely pathogenic Ehlers-Danlos syndrome, classic type, 1 2022-11-01 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL5A1 protein function. ClinVar contains an entry for this variant (Variation ID: 409092). This missense change has been observed in individuals with classic Ehlers-Danlos syndrome (PMID: 19370768). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 1835 of the COL5A1 protein (p.Cys1835Ser).
GeneDx RCV004767268 SCV005376808 uncertain significance not provided 2024-04-15 criteria provided, single submitter clinical testing Has been reported in an individual with clinical features of classical EDS (PMID: 19370768); 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; Not located in the triple helical region, where the majority of pathogenic missense variants occur (PMID: 22696272; HGMD); This variant is associated with the following publications: (PMID: 22696272, 19370768)

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