Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003764547 | SCV004571519 | likely pathogenic | Partial hypoxanthine-guanine phosphoribosyltransferase deficiency; Lesch-Nyhan syndrome | 2023-02-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 161 of the HPRT1 protein (p.Ala161Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with HPRT1-related conditions (PMID: 2928313, 27288985). ClinVar contains an entry for this variant (Variation ID: 10041). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects HPRT1 function (PMID: 2928313). This variant disrupts the p.Ala161 amino acid residue in HPRT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11018746, 15386453, 19016344). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
OMIM | RCV000010736 | SCV000030962 | pathogenic | Partial hypoxanthine-guanine phosphoribosyltransferase deficiency | 1989-07-01 | no assertion criteria provided | literature only | |
OMIM | RCV000010737 | SCV000030963 | other | HPRT MILWAUKEE | 2020-09-10 | no assertion criteria provided | literature only |