ClinVar Miner

Submissions for variant NM_014362.4(HIBCH):c.365A>G (p.Tyr122Cys) (rs121918329)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623332 SCV000741820 likely pathogenic Inborn genetic diseases 2016-10-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224374 SCV000281100 pathogenic not provided 2015-09-17 criteria provided, single submitter clinical testing
GeneDx RCV000224374 SCV000491308 pathogenic not provided 2018-06-06 criteria provided, single submitter clinical testing The Y122C variant in the HIBCH gene has been reported previously in the compound heterozygous state with a splicing variant in a patient with 3-hydroxyisobutyryl-CoA hydrolase deficiency who exhibited hypotonia, poor feeding, developmental delay and regression, ketoacidosis, and basal ganglia abnormalities (Loupatty et al., 2007). The Y122C variant is in 15/245850 (0.006%) alleles in large population cohorts, with no homozygotes observed (Lek et al., 2016). The Y122C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Functional studies indicate that Y122C demonstrates normal protein expression with reduced enzyme activity (Loupatty et al., 2007). We interpret Y122C as a pathogenic variant.
OMIM RCV000001204 SCV000021354 pathogenic Beta-hydroxyisobutyryl-CoA deacylase deficiency 2007-01-01 no assertion criteria provided literature only
SIB Swiss Institute of Bioinformatics RCV000001204 SCV000883163 likely pathogenic Beta-hydroxyisobutyryl-CoA deacylase deficiency 2018-10-15 criteria provided, single submitter curation This variant is interpreted as Likely Pathogenic, for 3-hydroxyisobutryl-CoA hydrolase deficiency, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3-Moderate => PS3 downgraded in strength to Moderate. PM3-Supporting => PM3 downgraded in strength to Supporting.

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