ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.1787G>A (p.Arg596His)

gnomAD frequency: 0.00001  dbSNP: rs1057524199
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433038 SCV000534833 uncertain significance not provided 2020-05-06 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; 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 RCV000433038 SCV002168302 uncertain significance not provided 2021-02-20 criteria provided, single submitter clinical testing 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. This sequence change replaces arginine with histidine at codon 596 of the COL2A1 protein (p.Arg596His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL2A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 391702). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004816664 SCV005069411 uncertain significance Optic atrophy 2022-01-01 no assertion criteria provided clinical testing

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