Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000483629 | SCV000566696 | uncertain significance | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528) |
Ambry Genetics | RCV000491516 | SCV000579822 | benign | Hereditary cancer-predisposing syndrome | 2023-08-25 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Invitae | RCV003766666 | SCV000647591 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1829 of the APC protein (p.Asn1829Ser). This variant is present in population databases (rs767612847, 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: 419113). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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, |
RCV000491516 | SCV000909603 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-28 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 1829 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 10/250734 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, |
RCV001731707 | SCV001983739 | uncertain significance | not specified | 2021-09-16 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000483629 | SCV002046951 | uncertain significance | not provided | 2021-04-22 | criteria provided, single submitter | clinical testing |