ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.5317C>T (p.Pro1773Ser) (rs192863857)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000209980 SCV000265709 uncertain significance Malignant hyperthermia, susceptibility to, 1 2013-07-01 criteria provided, single submitter research
PreventionGenetics,PreventionGenetics RCV000241839 SCV000304958 benign not specified 2016-04-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000209980 SCV000412233 benign Malignant hyperthermia, susceptibility to, 1 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000400180 SCV000412234 benign Minicore myopathy 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000314530 SCV000412235 likely benign Neuromuscular disease, congenital, with uniform type 1 fiber 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000362258 SCV000412236 likely benign Central core myopathy 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000766302 SCV000617090 uncertain significance not provided 2017-10-23 criteria provided, single submitter clinical testing The P1773S variant has been reported in an individual who did not have a personal or family history of an RYR1-related disorder (Gonsalves et al., 2013). The P1773S variant is observed in 272/18,786 (1.4%) alleles from individuals of East Asian background, which is greater than expected for this disorder (Lek et al., 2016). However, this variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function.
Invitae RCV001082672 SCV001002800 benign RYR1-Related Disorders 2019-12-31 criteria provided, single submitter clinical testing

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