ClinVar Miner

Submissions for variant NM_000190.4(HMBS):c.518G>A (p.Arg173Gln)

dbSNP: rs118204096
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001851550 SCV002239477 pathogenic not provided 2023-03-17 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with acute intermittent porphyria (PMID: 2243128, 9281416). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 173 of the HMBS protein (p.Arg173Gln). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 1447). 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. Experimental studies have shown that this missense change affects HMBS function (PMID: 9281416). This variant disrupts the p.Arg173 amino acid residue in HMBS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1301948, 7635464, 11399210, 15643298, 23815679). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001512 SCV000021667 pathogenic Acute intermittent porphyria 1992-01-01 no assertion criteria provided literature only
OMIM RCV003764511 SCV004697360 pathogenic Encephalopathy, porphyria-related 1992-01-01 no assertion criteria provided literature only

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