Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003474735 | SCV000166065 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2721 of the APC protein (p.Arg2721His). This variant is present in population databases (rs587780606, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 135723). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. 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. |
| Ambry Genetics | RCV000218426 | SCV000276416 | likely benign | Hereditary cancer-predisposing syndrome | 2022-11-28 | 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. |
| Gene |
RCV000479454 | SCV000572792 | uncertain significance | not provided | 2023-06-30 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25545608, 27499925, 18199528, 29684080, 28944238) |
| Color Diagnostics, |
RCV000218426 | SCV000904044 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-26 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with histidine at codon 2721 of the APC 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 as germline in an individual affected with uterine carcinosarcoma (PMID: 29684080). This variant has been identified in 3/251312 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. |
| Revvity Omics, |
RCV000479454 | SCV003826831 | uncertain significance | not provided | 2019-09-23 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003474735 | SCV004202814 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-04 | criteria provided, single submitter | clinical testing |