ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.14173G>C (p.Val4725Leu)

dbSNP: rs1049117716
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000692536 SCV000820363 uncertain significance RYR1-related disorder 2022-07-06 criteria provided, single submitter clinical testing 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. 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: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 571399). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 4725 of the RYR1 protein (p.Val4725Leu).
Fulgent Genetics, Fulgent Genetics RCV000764200 SCV000895203 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion 2018-10-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000692536 SCV002540238 uncertain significance RYR1-related disorder 2022-01-05 criteria provided, single submitter clinical testing The RYR1 c.14173G>C (p.Val4725Leu) missense variant results in the substitution of valine at amino acid position 4725 with leucine. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Based on the available evidence, the c.14173G>C (p.Val4725Leu) variant is classified as a variant of uncertain significance for RYR1-related disorders.
Revvity Omics, Revvity RCV003133534 SCV003812451 uncertain significance not provided 2021-10-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003999585 SCV004832708 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces valine with leucine at codon 4725 of the RYR1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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