Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004564696 | SCV001380061 | uncertain significance | Familial adenomatous polyposis 1 | 2024-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 2481 of the APC protein (p.Thr2481Ser). This variant is present in population databases (no rsID available, gnomAD 0.02%). 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: 939283). 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. |
| Prevention |
RCV003398936 | SCV004110169 | uncertain significance | APC-related disorder | 2023-04-13 | criteria provided, single submitter | clinical testing | The APC c.7441A>T variant is predicted to result in the amino acid substitution p.Thr2481Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 2 of ~31,000 alleles in individuals in gnomAD (http://gnomad.broadinstitute.org/variant/5-112178732-A-T) and is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/939283/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| All of Us Research Program, |
RCV004010669 | SCV004824482 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2023-06-26 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with serine at codon 2481 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 not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 2/31378 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. |
| Ambry Genetics | RCV004944868 | SCV005465456 | likely benign | Hereditary cancer-predisposing syndrome | 2024-09-08 | 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. |