Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000464936 | SCV000543763 | likely benign | Juvenile polyposis syndrome | 2025-01-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002311769 | SCV000671972 | likely benign | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2023-04-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Color Diagnostics, |
RCV000570776 | SCV000691419 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with leucine at codon 156 of the SMAD4 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with colorectal cancer in the literature (PMID: 28944238). This variant has been identified in 5/282804 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781854 | SCV000920227 | uncertain significance | not specified | 2020-08-24 | criteria provided, single submitter | clinical testing | Variant summary: SMAD4 c.466A>T (p.Met156Leu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251400 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.466A>T in individuals affected with Juvenile Polyposis Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Gene |
RCV001566748 | SCV001790314 | uncertain significance | not provided | 2024-11-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18823382, 22992590, 15235019, 36315513, 28944238, 33939675) |
| Sema4, |
RCV000570776 | SCV002538327 | likely benign | Hereditary cancer-predisposing syndrome | 2021-02-17 | criteria provided, single submitter | curation |