Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003315716 | SCV000282833 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2611 of the APC protein (p.Thr2611Ile). This variant is present in population databases (rs587778037, gnomAD 0.02%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 27978560). ClinVar contains an entry for this variant (Variation ID: 133523). 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. |
Counsyl | RCV000230402 | SCV000487898 | uncertain significance | Familial adenomatous polyposis 1 | 2015-12-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586315 | SCV000694126 | uncertain significance | not provided | 2017-02-23 | criteria provided, single submitter | clinical testing | Variant summary: The APC c.7832C>T (p.Thr2611Ile) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this substitution (SNPs&GO not captured due to low reliability index). This variant was found in 1/122206 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714). It was reported in at least one CRC patient, however without strong evidence for pathogenicity such as co-segregation. Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS. |
Color Diagnostics, |
RCV000774673 | SCV000908557 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-09 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with isoleucine at codon 2611 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with rectal cancer (PMID: 27978560), as well as in an unaffected individual (PMID: 24728327). This variant has been identified in 3/250108 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. |
Laboratory for Molecular Medicine, |
RCV000120033 | SCV000966579 | uncertain significance | not specified | 2018-10-16 | criteria provided, single submitter | clinical testing | The p.Thr2611Ile variant in APC has been reported in at least one individual wit h colorectal cancer (Pearlman 2017) and at least one healthy individual undergoi ng multi-gene sequencing (Bodian 2015). This variant has also been reported by o ther clinical laboratories in ClinVar (Variation ID: 133523). Additionally, this variant has been identified in 3/17232 East Asian chromosomes by gnomAD (http:/ /gnomad.broadinstitute.org). Computational prediction tools and conservation ana lysis suggest that the p.Thr2611Ile variant may impact the protein. In summary, the clinical significance of the p.Thr2611Ile variant is uncertain. ACMG/AMP Cri teria applied: PP3. |
Ambry Genetics | RCV000774673 | SCV001189323 | likely benign | Hereditary cancer-predisposing syndrome | 2021-10-29 | 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. |
Sema4, |
RCV000774673 | SCV002530889 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-08 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV003315716 | SCV004018784 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-21 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
ITMI | RCV000120033 | SCV000084164 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
3DMed Clinical Laboratory Inc | RCV000677760 | SCV000803916 | uncertain significance | Colon adenocarcinoma | 2017-08-18 | no assertion criteria provided | clinical testing |