Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002036111 | SCV002310926 | uncertain significance | Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 397 of the AHCY protein (p.Ala397Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs202122223, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with AHCY-related conditions. ClinVar contains an entry for this variant (Variation ID: 1522574). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AHCY protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004044776 | SCV004875178 | uncertain significance | Inborn genetic diseases | 2023-12-14 | criteria provided, single submitter | clinical testing | The c.1190C>T (p.A397V) alteration is located in exon 10 (coding exon 10) of the AHCY gene. This alteration results from a C to T substitution at nucleotide position 1190, causing the alanine (A) at amino acid position 397 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |