Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001051587 | SCV001215751 | likely pathogenic | Partial hypoxanthine-guanine phosphoribosyltransferase deficiency; Lesch-Nyhan syndrome | 2019-12-28 | criteria provided, single submitter | clinical testing | 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. 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: 19016344, 15386453, 11018746). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant has been observed in individuals with HPRT1-related conditions (PMID: 19016344, 25136576). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 161 of the HPRT1 protein (p.Ala161Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. |