Submissions for variant NM_000190.4(HMBS):c.962G>A (p.Arg321His)

dbSNP: rs150428209

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000148508	SCV000367707	likely benign	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Eurofins Ntd Llc (ga)	RCV000730694	SCV000858452	uncertain significance	not provided	2017-11-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000730694	SCV001051958	likely benign	not provided	2025-02-02	criteria provided, single submitter	clinical testing
Mount Sinai Diagnostic Laboratory, Icahn School of Medicine at Mount Sinai	RCV000148508	SCV001132051	benign	Acute intermittent porphyria		criteria provided, single submitter	research
GeneDx	RCV000730694	SCV001764085	likely benign	not provided	2020-10-27	criteria provided, single submitter	clinical testing	Reported previously in a 36-year-old Swiss male with acute intermittent porphyria and low-normal hydroxymethylbilane synthase (aka PBG deaminase) activity (Schuurmans et al., 2001); Reported in cis with an HMBS splicing variant in a 63-year-old German male with abdominal pain, paralytic attacks of the right extremities, depression, and reduced hydroxymethylbilane synthase activity that was 40% of normal levels (von Brasch et al., 2004); Published functional studies demonstrate no damaging effect (Lenglet et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30556376, 29360981, 22190498, 27769855, 26075277, 17298216, 27539938, 11591889, 25637381, 15003823)
CSER _CC_NCGL, University of Washington	RCV000148508	SCV000190219	likely benign	Acute intermittent porphyria	2014-06-01	no assertion criteria provided	research
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000730694	SCV001807788	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000730694	SCV001955990	likely benign	not provided		no assertion criteria provided	clinical testing