ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.10219G>A (p.Ala3407Thr) (rs143533100)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513119 SCV000608902 uncertain significance not provided 2017-03-31 criteria provided, single submitter clinical testing
GeneDx RCV000513119 SCV000569485 uncertain significance not provided 2017-02-23 criteria provided, single submitter clinical testing The A3407T variant in the RYR1 gene has been reported previously in association with exercise-induced rhabdomyolysis in an affected individual who was compound heterozygous for the A3407T variant and another missense variant in the RYR1 gene (Snoeck et al., 2015). The A3407T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A3407T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (C3402G, P3410Q) and at the same residue (A3407S) have been reported in the Human Gene Mutation Database in association with RYR1-related disorders (Stenson et al., 2014), suggesting functional importance for this region of the protein. We interpret A3407T as a variant of uncertain significance.
GenomeConnect, ClinGen RCV000509306 SCV000607369 not provided RYR1-Related Disorder no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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