Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000791929 | SCV000931198 | pathogenic | not provided | 2023-09-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects HMBS function (PMID: 30740734). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HMBS protein function. ClinVar contains an entry for this variant (Variation ID: 639190). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 240 of the HMBS protein (p.Asp240Gly). This missense change has been observed in individual(s) with acute intermittent porphyria (PMID: 30740734; Invitae; personalcommunicationMt.Sinai). This variant is not present in population databases (gnomAD no frequency). |