ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.112G>A (p.Ala38Thr)

dbSNP: rs377558801
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000815396 SCV000955846 uncertain significance RYR1-related disorder 2022-08-30 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 38 of the RYR1 protein (p.Ala38Thr). This variant is present in population databases (rs377558801, gnomAD 0.03%). This missense change has been observed in individual(s) with nemaline rod myopathy (PMID: 34000440). ClinVar contains an entry for this variant (Variation ID: 658548). 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 not 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 RCV002495150 SCV002784171 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 2021-08-31 criteria provided, single submitter clinical testing
GeneDx RCV003442108 SCV004169653 uncertain significance not provided 2023-10-19 criteria provided, single submitter clinical testing Reported heterozygous in an individual with nemaline rod myopathy who harbored variants in several additional genes in published literature (Usha Devi et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33767344, 34000440)

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