ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.6860C>A (p.Ala2287Asp)

gnomAD frequency: 0.00002  dbSNP: rs761154999
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001943281 SCV002182203 uncertain significance RYR1-related disorder 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 2287 of the RYR1 protein (p.Ala2287Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is present in population databases (rs761154999, ExAC 0.003%). This missense change has been observed in individual(s) with congenital myopathy (PMID: 30611313). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR1 protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002484475 SCV002779973 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-07-27 criteria provided, single submitter clinical testing

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