ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.6910G>A (p.Gly2304Ser) (rs377080876)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000353321 SCV000412382 uncertain significance Central core myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000267871 SCV000412383 uncertain significance Multiminicore Disease 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000304664 SCV000412384 uncertain significance Neuromuscular disease, congenital, with uniform type 1 fiber 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000359403 SCV000412385 uncertain significance Malignant hyperthermia susceptibility 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000655539 SCV000777470 uncertain significance RYR1-Related Disorders 2019-10-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2304 of the RYR1 protein (p.Gly2304Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs377080876, ExAC 0.07%). This variant has not been reported in the literature in individuals with RYR1-related disease. ClinVar contains an entry for this variant (Variation ID: 329056). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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