Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000229513 | SCV000290749 | uncertain significance | Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 60 of the WT1 protein (p.Gly60Arg). This variant is present in population databases (rs374404615, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with WT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 241478). 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 arginine 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. |
Illumina Laboratory Services, |
RCV001104737 | SCV001261623 | uncertain significance | Wilms tumor 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV001105881 | SCV001262894 | uncertain significance | Nephrotic syndrome, type 4 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV001105882 | SCV001262895 | uncertain significance | Meacham syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Gene |
RCV001563568 | SCV001786538 | likely benign | not provided | 2023-07-24 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Institute for Clinical Genetics, |
RCV001563568 | SCV002011019 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001820764 | SCV002072258 | uncertain significance | not specified | 2021-01-08 | criteria provided, single submitter | clinical testing | This sequence change does not appear to have been previously described in patients with WT1-related disorders and has been described in the gnomAD database with a low population frequency of 0.048% in the non-Finnish European subpopulation (dbSNP rs374404615). The p.Gly65Arg change affects a poorly conserved amino acid residue located in a domain of the WT1 protein that is not known to be functional. The p.Gly65Arg substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Gly65Arg change remains unknown at this time. |
Sema4, |
RCV002257598 | SCV002530530 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002519803 | SCV003677616 | likely benign | Inborn genetic diseases | 2022-12-06 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Genome Diagnostics Laboratory, |
RCV001563568 | SCV001928534 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001563568 | SCV001965702 | likely benign | not provided | no assertion criteria provided | clinical testing |