ClinVar Miner

Submissions for variant NM_000411.8(HLCS):c.1741G>A (p.Gly581Ser) (rs119103230)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000001987 SCV000756234 pathogenic Holocarboxylase synthetase deficiency 2017-12-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 581 of the HLCS protein (p.Gly581Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs119103230, ExAC 0.003%). This variant has been reported as homozygous or in combination with another HLCS variant in individuals affected with holocarboxylase synthetase deficiency (PMID: 10190325, 12124727). ClinVar contains an entry for this variant (Variation ID: 1910). This variant has been observed on the opposite chromosome (in trans) from a likely pathogenic variant in an individual affected with holocarboxylase synthetase deficiency (PMID: 12124727). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Experimental studies have shown that this missense change reduces HLCS enzymatic activity in vitro (PMID: 10190325, 24239178). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001987 SCV000022145 pathogenic Holocarboxylase synthetase deficiency 2001-11-01 no assertion criteria provided literature only

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