Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000084001 | SCV005400215 | pathogenic | Hydatidiform mole, recurrent, 1 | 2023-12-21 | 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 the likely mechanism of disease in this gene and is associated with hydatidiform mole, recurrent 1 (MIM#231090). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0113 - This gene is postulated to be associated with a maternal multi-locus imprinting defect (PMID: 35842788). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to tryptophan. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2; 15 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2; 12 heterozygotes, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. However, this residue is well-conserved in primates and in silico tools are unreliable due to lineage-specific evolution (PMID: 19682372). (I) 0600 - Variant is located in the leucine-rich region (PMID: 19246479). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as homozygous or compound heterozygous in at least 6 unrelated individuals with recurrent atypical hydatidiform moles (PMID 26956250; PMID 19246479; PMID 21439709; PMID 26544189; PMID: 36001209; PMID: 32484253). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1101 - Very strong and specific 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 |
| Unité médicale des maladies autoinflammatoires, |
RCV000084001 | SCV000116123 | not provided | Hydatidiform mole, recurrent, 1 | no assertion provided | not provided |