Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000114353 | SCV002301951 | uncertain significance | Aicardi-Goutieres syndrome 5 | 2022-05-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 145 of the SAMHD1 protein (p.Arg145Gln). This variant is present in population databases (rs515726145, gnomAD 0.003%). This missense change has been observed in individual(s) with Aicardi-Goutieres syndrome (PMID: 19525956). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 126412). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects SAMHD1 function (PMID: 22461318, 28229507). 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. |
| Institute of Human Genetics, |
RCV003390795 | SCV004101807 | likely pathogenic | not provided | 2023-11-14 | criteria provided, single submitter | clinical testing | This variant has been identified by standard clinical testing. Selected ACMG criteria: Likely pathogenic (V):PP3;PP2;PM5;PM2 |
| Gene |
RCV000114353 | SCV000147933 | not provided | Aicardi-Goutieres syndrome 5 | no assertion provided | literature only |