ClinVar Miner

Submissions for variant NM_003140.3(SRY):c.226C>T (p.Arg76Cys)

dbSNP: rs2124486234
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002001650 SCV002276505 uncertain significance 46,XY sex reversal 1 2020-12-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 76 of the SRY protein (p.Arg76Cys). The arginine residue is weakly 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 clinical features of 46XY sex reversal (Invitae). 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. This variant disrupts the p.Arg76 amino acid residue in SRY. Other variant(s) that disrupt this residue have been observed in individuals with SRY-related conditions (PMID: 10670762, Invitae), which suggests that this may be a clinically significant amino acid residue. 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.

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