Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004790092 | SCV005400031 | uncertain significance | Early-onset myopathy with fatal cardiomyopathy | 2022-09-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is known mechanism of disease in this gene. In addition, dominant-negative is also a suggested mechanism (PMID: 25589632). (I) 0108 - This gene is associated with both recessive and dominant disease (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance. Variants in this gene that result in a premature truncating codon (PTC) are known to have reduced penetrance in DCM (PMID: 25589632). (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0506 - Abnormal splicing is not predicted and nucleotide is poorly conserved. (SB) 0600 - Variant is located in the annotated I band, where adjacent exons have PSI scores of 54 and 59 (cardiodb). (I) 0705 - No comparable non-canonical splice variants have previous evidence for pathogenicity. (I) 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 |