Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001381874 | SCV001580442 | pathogenic | not provided | 2024-11-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 111 of the HMBS protein (p.Gly111Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with acute intermittent porphyria (PMID: 8268934, 11399210, 11857754). ClinVar contains an entry for this variant (Variation ID: 1464). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on HMBS protein function. Experimental studies have shown that this missense change affects HMBS function (PMID: 8268934, 29360981). For these reasons, this variant has been classified as Pathogenic. |
MGZ Medical Genetics Center | RCV000001529 | SCV002580038 | likely pathogenic | Acute intermittent porphyria | 2022-06-01 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000001529 | SCV000021684 | pathogenic | Acute intermittent porphyria | 1994-01-01 | no assertion criteria provided | literature only |