Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000810491 | SCV000950694 | likely pathogenic | Partial hypoxanthine-guanine phosphoribosyltransferase deficiency; Lesch-Nyhan syndrome | 2018-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 204 of the HPRT1 protein (p.His204Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Lesch-Nyhan syndrome (PMID: 9799086). This variant is also known as p.His203Tyr in the literature. 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 C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.His204 (also known as p.His203 in the literature) amino acid residue in HPRT1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 16549399, 2928313, 22157001, 25481104, 2071157, 23975452), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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. |