Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetics and Molecular Pathology, |
RCV000001654 | SCV004175321 | pathogenic | Hydatidiform mole, recurrent, 1 | 2023-07-18 | criteria provided, single submitter | clinical testing | The NLRP7 c.2078G>C variant is classified as PATHOGENIC (PM5, PM3_Strong, PP1_Strong, PS3_Supporting, PP4). The NLRP7 c.2078G>C variant is a single nucleotide change in exon 5/11 of the NLRP7 gene, which is predicted to change the amino acid arginine at position 693 in the protein to proline. This variant is a missense change at an amino acid residue where two different pathogenic missense changes have been seen before: p.(Arg693Gln) and p.(Arg693Trp) (ClinVar Variation IDs: 1591, 1586) (PM5). This variant has been detected homozygous or compound heterozygous with a pathogenic variant in multiple unrelated families (PMID: 16462743, 19246479) (PM3_Strong). This variant co-segregates with disease and has been detected homozogyous or compound heterozygous with a pathogenic variant in six unrelated, non-consanguineous Indian/Pakistani families. Haplotype analysis showed a common haplotype associated with the pathogenic variant, suggesting a potential founder mutation (PMID: 19650864) (PP1_Strong). Genome-wide methylation studies on molar tissue from two sisters homozygous for the variant demonstrated aberrant methylation at maternal differentially methylated regions compared to non-molar normal placental tissue (PMID: 26544189) (PS3_Supporting). The clinical history is highly specific for the NLRP7 gene (PP4). The variant has been reported in dbSNP (rs104895502) and is present in population databases (gnomAD v3.1.2 allele frequency = 0.002%, 3 het/152030 alleles). It is reported as disease causing in the HGMD database (CM061147) and is reported as Pathogenic by other diagnostic laboratories (ClinVar Variation ID: 1587). |
| OMIM | RCV000001654 | SCV000021810 | pathogenic | Hydatidiform mole, recurrent, 1 | 2009-09-01 | no assertion criteria provided | literature only | |
| Unité médicale des maladies autoinflammatoires, |
RCV000001654 | SCV000116108 | not provided | Hydatidiform mole, recurrent, 1 | no assertion provided | not provided |