ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.7111G>A (p.Glu2371Lys)

dbSNP: rs1057518940
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000414976 SCV000492979 pathogenic Short stature; Delayed gross motor development; Congenital contracture; Proximal amyotrophy 2014-04-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001198534 SCV001369509 pathogenic Congenital myopathy with fiber type disproportion 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic.
Invitae RCV001233334 SCV001405922 pathogenic RYR1-related disorder 2023-05-09 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2371 of the RYR1 protein (p.Glu2371Lys). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu237 amino acid residue in RYR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19191333). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 374164). This missense change has been observed in individual(s) with clinical features of autosomal dominant RYR1-related myopathy (PMID: 32403337, 33333461, 34106991; Invitae). In at least one individual the variant was observed to be de novo.
Revvity Omics, Revvity RCV003133254 SCV003812403 uncertain significance not provided 2019-11-20 criteria provided, single submitter clinical testing

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