ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.823C>T (p.Arg275Cys) (rs121912876)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000988828 SCV001138713 pathogenic Stickler syndrome type 1 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001385337 SCV001585157 pathogenic not provided 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 275 of the COL2A1 protein (p.Arg275Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with COL2A1-related conditions (PMID: 8244341, 32071555). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17368). This variant is also known as p.Arg75Cys in the literature. 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 expected to disrupt COL2A1 protein function. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001385337 SCV001814714 pathogenic not provided 2020-10-22 criteria provided, single submitter clinical testing 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; In addition, in silico splice predictors suggest this variant may lead to abnormal gene splicing; This variant is associated with the following publications: (PMID: 8244341, 32071555, 18553548, 19764028, 15593085, 23928235, 17726487, 16755660, 23448908, 8877930, 7738948, 21990059, 8024616, 18383211, 21332586, 21472893, 21356074, 19433093, 25735649, 21204228, 26183434, 28334714, 27234559, 29738498, 21438135, 22791362, 16155195, 27523816, 26691295, 26443184, 31758797, 31711313, 31633310, 31894489, 7757086)
Blueprint Genetics RCV001385337 SCV001832467 pathogenic not provided 2019-11-30 criteria provided, single submitter clinical testing
OMIM RCV000018912 SCV000039196 pathogenic Czech dysplasia, metatarsal type 2009-10-01 no assertion criteria provided literature only

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