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

gnomAD frequency: 0.00001  dbSNP: rs267607206

Total submissions: 2

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