Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001926947 | SCV002198862 | uncertain significance | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with DVL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 441 of the DVL1 protein (p.Glu441Asp). |
| Victorian Clinical Genetics Services, |
RCV002471188 | SCV002767217 | likely benign | Autosomal dominant Robinow syndrome 2 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Benign. Following criteria are met: 0101 - Gain of function is a known mechanism of disease in this gene and is associated with autosomal dominant Robinow syndrome 2 (MIM#616331). Pathogenic truncating variants that escape nonsense-mediated decay (NMD) have been shown to result in increased canonical WNT activity (PMID: 25817014, PMID: 25817016). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to aspartic acid. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools and not conserved in placental mammals with a minor amino acid change. (SB) 0600 - Variant is located in the annotated DEP dishevelled domain (NCBI). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0904 - Non-segregation of this variant with the phenotype under investigation has been clearly demonstrated. The variant has been shown to be inherited from this individual's clinically unaffected parent. (SB) 1007 - No published functional evidence has been identified for this variant. (I) 1102 - Strong phenotype match for this individual. (SP) 1206 - This variant has been shown to be paternally inherited (by segregation testing). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |