ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.602C>A (p.Ser201Tyr) (rs760106433)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672903 SCV000798055 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2018-02-21 criteria provided, single submitter clinical testing
GeneDx RCV000522404 SCV000616740 pathogenic not provided 2017-07-25 criteria provided, single submitter clinical testing The S201Y variant in the HMGCL gene has previously been reported in association with HMG-CoA lyase deficiency in an individual who was homozygous for S201Y (Casals et al., 2003). Functional anaylsis of S201Y found that it is associated with no detectable residual enzyme activity (Casals et al., 2003). The S201Y variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S201Y variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some 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. In summary, we interpret S201Y to be a pathogenic variant.

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