ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12313C>T (p.Leu4105Phe)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002472126 SCV002768551 likely pathogenic Catecholaminergic polymorphic ventricular tachycardia 1 2020-07-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 4-Likely Pathogenic. Following criteria are met: 0101 - Gain-of-function is a known mechanism of disease for this gene (PMID: 19926015). (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from leucine to phenylalanine (exon 90). (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0309 - An alternative amino acid change to isoleucine at the same position has been observed in gnomAD (v2: 1 heterozygote, 0 homozygotes). (N) 0501 - Missense variant consistently predicted to be damaging by multiple in-silico tools or highly conserved with a major amino acid change. (P) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants (Domain III - Channel Region; PMID: 19926015). (P) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0802 - Moderate previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported in patients with catecholaminergic polymorphic ventricular tachycardia (PMID: 18849218, 23595086). (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
GeneDx RCV004593035 SCV005081212 uncertain significance not provided 2023-12-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18849218, 24025405, 23595086, 29434162, 32152366)

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