ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.13022C>T (p.Thr4341Met) (rs752855919)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000415733 SCV000493461 uncertain significance not provided 2016-07-31 criteria provided, single submitter clinical testing
Invitae RCV000808483 SCV000948593 uncertain significance RYR1-Related Disorders 2018-10-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 4341 of the RYR1 protein (p.Thr4341Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with RYR1-related disease. ClinVar contains an entry for this variant (Variation ID: 374619). 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: "Tolerated"; PolyPhen-2: "Not Available"; 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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