ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7027G>A (p.Gly2343Ser) (rs536596969)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000655584 SCV000777515 uncertain significance RYR1-Related Disorders 2018-06-15 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2343 of the RYR1 protein (p.Gly2343Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant also falls at the last nucleotide of exon 43 of the RYR1 coding sequence, which is part of the consensus splice site for this exon. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). This variant is present in population databases (rs536596969, ExAC 0.009%). This variant has been reported in a family affected with centronuclear myopathy (PMID: 28818389). ClinVar contains an entry for this variant (Variation ID: 544443). 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 disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
NeuroMeGen,Hospital Clinico Santiago de Compostela RCV000754734 SCV000882622 likely pathogenic Myopathy, Central Core 2018-10-08 criteria provided, single submitter clinical testing

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