Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004789792 | SCV005400468 | likely pathogenic | Focal segmental glomerulosclerosis 2 | 2024-10-10 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Likely pathogenic. Following criteria are met: 0101 - Gain of function is a known mechanism of disease in this gene and is associated with glomerulosclerosis, focal segmental, 2 (MIM#603965). Reported variants are associated with current amplitude amplification and/or delay of the channel inactivation which results in a gain of function mechanism (PMID: 15879175, PMID: 32509715, PMID: 31266820). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (v2, v3, and v4). (SP) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants. This variant is located in a cluster of pathogenic protein truncating variants (PTCs) and missense variants in the coiled-coil domain (DECIPHER, PMID: 23663351, PMID: 31936014). Dysfunctional coiled-coil assembly due to both missense and truncating variants in mutated TRPC6 disrupts calmodulin bridging which is essential for Ca2+-dependent inactivation (PMID: 31266820). (SP) 0705 - No comparable protein truncating 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) 1102 - Strong phenotype match for this individual. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |