ClinVar Miner

Submissions for variant NM_024884.3(L2HGDH):c.293A>G (p.His98Arg) (rs267607206)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522298 SCV000617755 likely pathogenic not provided 2017-10-05 criteria provided, single submitter clinical testing The H98R variant in the L2HGDH gene has been reported previously in the heterozygous state, in the presence of a second L2HGDH variant, and in the homozygous state, in multiple unrelated individuals with L-2-hydroxyglutaric aciduria, intellectual disability, and leukodystrophy (Vilarinho et al., 2005; Vilarinho et al., 2010). A different missense variant at the same residue, H98Y, has also been reported in the homozygous state in individuals with L-2-hydroxyglutaric aciduria (Topçu et al., 2004; Haliloglu et al., 2008). The H98R variant is not observed in large population cohorts (Lek et al., 2016). The H98R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret H98R as a likely pathogenic variant.
OMIM RCV000001679 SCV000021835 pathogenic L-2-hydroxyglutaric aciduria 2010-01-01 no assertion criteria provided literature only

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