ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7244G>A (p.Arg2415Gln) (rs201584482)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genetic Medicine Research,Children's National Medical Center RCV000226037 SCV000265813 uncertain significance not specified 2015-12-01 criteria provided, single submitter research
CeGaT Praxis fuer Humangenetik Tuebingen RCV000996888 SCV001151862 uncertain significance not provided 2019-03-01 criteria provided, single submitter clinical testing
Invitae RCV001222723 SCV001394839 uncertain significance RYR1-Related Disorders 2019-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2415 of the RYR1 protein (p.Arg2415Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs201584482, ExAC 0.03%). This variant has been observed in an individual affected with a RYR1-related condition (PMID: 27854218). ClinVar contains an entry for this variant (Variation ID: 224694). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This missense change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. 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.

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