ClinVar Miner

Submissions for variant NM_000687.4(AHCY):c.266C>T (p.Ala89Val)

gnomAD frequency: 0.00002  dbSNP: rs755222515
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622679 SCV000742930 uncertain significance Inborn genetic diseases 2017-09-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005091815 SCV005838911 likely pathogenic Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase 2024-12-09 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 89 of the AHCY protein (p.Ala89Val). This variant is present in population databases (rs755222515, gnomAD 0.003%). This missense change has been observed in individual(s) with AHCY-related conditions and/or S-Adenosylhomocysteine hydrolase deficiency (PMID: 16736098, 28779239, 33072517). ClinVar contains an entry for this variant (Variation ID: 522065). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt AHCY protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects AHCY function (PMID: 28647132). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Yale Center for Mendelian Genomics, Yale University RCV000662291 SCV000784619 likely pathogenic Rhabdomyolysis 2017-08-05 no assertion criteria provided literature only

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