Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001837644 | SCV002098202 | pathogenic | not provided | 2022-02-13 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22522421, 23288328) |
| Victorian Clinical Genetics Services, |
RCV002471170 | SCV002768903 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2U | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (MIM#614643) and muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7 (MIM#616052). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v3) <0.01 for a recessive condition (18 heterozygotes, 0 homozygotes). It has been misannotated as p.(Ser19Glufs*97). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Multiple NMD-predicted variants have been reported as pathogenic, and observed in patients with limb girdle muscular dystrophy and/or Walker-Warburg syndrome (ClinVar, PMID: 28688748, PMID: 30060766, PMID: 22522420). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |