Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002470349 | SCV002767121 | uncertain significance | Retinitis pigmentosa 10 | 2020-05-26 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3C-VUS. Following criteria are met: 0102 - Loss-of-function is a likely mechanism of disease for this gene. In vitro assays demonstrated loss in nucleic acid binding, not enzymatic activities of the mutant protein (PMID: 16384941 ). (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine (exon 8) (N) 0251 - Variant is heterozygous. (N) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (4 heterozygotes, 0 homozygotes). (N) 0504 - Same amino acid change has been observed in mammals. (B) 0600 - Variant is located in an annotated domain or motif. In the CBS domain (PDB). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |
Labcorp Genetics |
RCV002571485 | SCV002945665 | uncertain significance | not provided | 2023-11-10 | 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 221 of the IMPDH1 protein (p.Arg221Gln). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with IMPDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1806065). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Prevention |
RCV004736173 | SCV005346578 | uncertain significance | IMPDH1-related disorder | 2024-08-16 | no assertion criteria provided | clinical testing | The IMPDH1 c.662G>A variant is predicted to result in the amino acid substitution p.Arg221Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00089% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |