Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004564120 | SCV000552731 | uncertain significance | Familial adenomatous polyposis 1 | 2024-09-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1595 of the APC protein (p.Ala1595Ser). 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: 411531). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Color Diagnostics, |
RCV000775710 | SCV000910125 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-18 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000775710 | SCV002634346 | likely benign | Hereditary cancer-predisposing syndrome | 2021-06-14 | 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. |
| Prevention |
RCV004722796 | SCV005339091 | uncertain significance | APC-related disorder | 2024-09-26 | no assertion criteria provided | clinical testing | The APC c.4783G>T variant is predicted to result in the amino acid substitution p.Ala1595Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD, which may been too common to be a primary cause of disease. This variant has been reported as likely benign and uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/411531/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |