Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000230402 | SCV000282833 | uncertain significance | Familial adenomatous polyposis 1 | 2018-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 2611 of the APC protein (p.Thr2611Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with colorectal cancer (PMID: 27978560). ClinVar contains an entry for this variant (Variation ID: 133523). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | |
| Integrated 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 | RCV000774673 | SCV000908557 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-11 | criteria provided, single submitter | clinical testing | |
| 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. |
| ITMI | RCV000120033 | SCV000084164 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
| 3DMed Clinical Laboratory Inc | RCV000677760 | SCV000803916 | uncertain significance | Adenocarcinoma of the colon | 2017-08-18 | no assertion criteria provided | clinical testing |