ClinVar Miner

Submissions for variant NM_000190.4(HMBS):c.500G>A (p.Arg167Gln) (rs118204095)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000001511 SCV000190221 uncertain significance Acute intermittent porphyria 2014-06-01 no assertion criteria provided research
GeneDx RCV000520560 SCV000616739 likely pathogenic not provided 2018-09-26 criteria provided, single submitter clinical testing The R167Q variant in the HMBS gene has been reported previously in the heterozygous state in association with acute intermittent porphyria (Delfau et al., 1990). R167Q has also been reported in the compound heterozygous state with another HMBS variant in affected individuals from two families with spasticity, ataxia, neuropathy, and abnormal head imaging findings (Llewellyn et al., 1992; Kevelam et al., 2016). Functional studies demonstrate that the R167Q variant results in a dramatic reduction in enzymatic activity to approximately 1% of wild type levels (Delfau et al., 1990; Chen et al., 2016). The R167Q variant is observed in 8/72,186 (0.01%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). The R167Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. We interpret R167Q as a likely pathogenic variant.
OMIM RCV000001511 SCV000021666 pathogenic Acute intermittent porphyria 1992-04-01 no assertion criteria provided literature only

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