ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1394A>C (p.Tyr465Ser) (rs1057520772)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000436944 SCV000517378 pathogenic not provided 2015-06-03 criteria provided, single submitter clinical testing The Y465S missense change was reported previously in a patient with weakness, hypotonia, calfhypertrophy, and elevated serum CK values who was homozygous for this variant. A muscle biopsy alsoshowed greatly diminished alpha-dystroglycan levels (Brockington et al., 2001). It was not observed inapproximately 6,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The Y465S variantis a semi-conservative amino acid substitution, which may impact secondary protein structure as theseresidues differ in some properties. This substitution occurs at a position that is conserved in mammals, andmultiple missense variants in nearby residues have been reported in the Human Gene Mutation Databasein association with FKRP-related disorders (Stenson et al., 2014), supporting the functional importance ofthis region of the protein. Therefore, Y465S is considered to be a pathogenic variant.

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