ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the p.Tyr127 amino acid residue in SRY have been observed in affected individuals (PMID: 12107262, 28787711). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. Experimental studies have shown that this missense change disrupts the ability of SRY to accumulate in the nucleus and bind to DNA in cell culture, but does not affect its interaction with calmodulin (PMID: 12409269, 20528776). This variant has been observed to be de novo in an individual affected with 46,XY disorder of sexual development (46,XY DSD) (Invitae) and has also been reported in the literature in an additional individual affected with 46, XY DSD (PMID: 8019555). ClinVar contains an entry for this variant (Variation ID: 470196). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 127 of the SRY protein (p.Tyr127Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine.