Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000001537 | SCV001265198 | uncertain significance | Acute intermittent porphyria | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Labcorp Genetics |
RCV002512652 | SCV003441181 | uncertain significance | not provided | 2023-04-12 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs118204113, gnomAD 0.002%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Ala252 amino acid residue in HMBS. Other variant(s) that disrupt this residue have been observed in individuals with HMBS-related conditions (PMID: 8262523, 9067752), which suggests that this may be a clinically significant amino acid residue. 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 not expected to disrupt HMBS protein function. ClinVar contains an entry for this variant (Variation ID: 1472). This missense change has been observed in individual(s) with acute intermittent porphyria (PMID: 8262523). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 252 of the HMBS protein (p.Ala252Thr). |
| Center for Genomic Medicine, |
RCV000001537 | SCV004807413 | uncertain significance | Acute intermittent porphyria | 2024-03-26 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000001537 | SCV000021692 | pathogenic | Acute intermittent porphyria | 1993-12-01 | no assertion criteria provided | literature only |