Total submissions: 21
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004737187 | SCV005367850 | benign | RYR1-related myopathy | 2024-08-07 | reviewed by expert panel | curation | The c.8589T>C (p.Ser2863=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by UCSC Genome Browser (BP4, BP7). The filtering allele frequency (the lower threshold of the 95% CI of 40732/91032, 9442 homozygotes) of the c.8589T>C variant in RYR1 is 0.4430 for South Asian chromosomes by gnomAD v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.00697) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for RYR1-related myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: BA1, BP4, BP7. (Congenital Myopathies VCEP specifications version 1; 8/7/2024) |
Eurofins Ntd Llc |
RCV000079178 | SCV000111047 | benign | not specified | 2014-06-06 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000079178 | SCV000194874 | benign | not specified | 2013-08-15 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000079178 | SCV000269791 | benign | not specified | 2015-01-13 | criteria provided, single submitter | clinical testing | p.Ser2863Ser in exon 55 of RYR1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 43.0% (1893/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2229146). |
Prevention |
RCV000079178 | SCV000305051 | benign | not specified | 2018-04-03 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000281789 | SCV000412584 | benign | Central core myopathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000339193 | SCV000412585 | benign | Malignant hyperthermia, susceptibility to, 1 | 2018-01-13 | 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 Laboratory Services, |
RCV000403926 | SCV000412586 | benign | Congenital multicore myopathy with external ophthalmoplegia | 2018-01-13 | 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 Laboratory Services, |
RCV000304127 | SCV000412587 | benign | Neuromuscular disease, congenital, with uniform type 1 fiber | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000079178 | SCV000519604 | benign | not specified | 2016-01-25 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Labcorp Genetics |
RCV001514067 | SCV001721816 | benign | RYR1-related disorder | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000281789 | SCV002032952 | benign | Central core myopathy | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001795076 | SCV002032953 | benign | King Denborough syndrome | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000403926 | SCV002032954 | benign | Congenital multicore myopathy with external ophthalmoplegia | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002490688 | SCV002794622 | benign | Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome | 2021-10-08 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000339193 | SCV004358157 | benign | Malignant hyperthermia, susceptibility to, 1 | 2019-03-29 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV000119753 | SCV005310839 | benign | not provided | criteria provided, single submitter | not provided | ||
Leiden Muscular Dystrophy |
RCV000119753 | SCV000154660 | not provided | not provided | no assertion provided | not provided | ||
Department of Pathology and Laboratory Medicine, |
RCV000119753 | SCV001554217 | uncertain significance | not provided | no assertion criteria provided | clinical testing | Allele frequency is common in at least one population database (frequency: 45.825% in gnomAD_Exomes) based on the frequency threshold of 2.223% for this gene. Variant was observed in a homozygous state in population databases more than expected for disease. 9 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation. A synonymous variant not located in a splice region. | |
Clinical Genetics, |
RCV000079178 | SCV001921729 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000079178 | SCV001951442 | benign | not specified | no assertion criteria provided | clinical testing |