Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV005037894 | SCV005666721 | pathogenic | Arterial calcification, generalized, of infancy, 1; Type 2 diabetes mellitus; Hypophosphatemic rickets, autosomal recessive, 2; Hypopigmentation-punctate palmoplantar keratoderma syndrome; Inherited obesity | 2024-03-18 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV005105262 | SCV005834523 | pathogenic | not provided | 2024-09-14 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 792 of the ENPP1 protein (p.Asn792Ser). This variant is present in population databases (rs370184526, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with autosomal recessive generalized arterial calcification of infancy (PMID: 12881724, 20016754). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ENPP1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ENPP1 function (PMID: 12881724). For these reasons, this variant has been classified as Pathogenic. |