Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410953 | SCV000489556 | uncertain significance | Familial adenomatous polyposis 1 | 2016-10-21 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000410953 | SCV000647784 | uncertain significance | Familial adenomatous polyposis 1 | 2022-02-21 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 292 of the APC protein (p.Leu292Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with non-medullary thyroid cancer (PMID: 26530882). ClinVar contains an entry for this variant (Variation ID: 372035). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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, |
RCV001178393 | SCV001342831 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-09 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with phenylalanine at codon 292 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with familial non-medullary thyroid cancer (PMID: 26530882). This variant has not been identified 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 | RCV001178393 | SCV002687238 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | The p.L292F variant (also known as c.876G>C), located in coding exon 8 of the APC gene, results from a G to C substitution at nucleotide position 876. The leucine at codon 292 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was detected in two non-medullary thyroid cancer patients from the same family (Yu Y et al. Sci Rep, 2015 Nov;5:16129). This amino acid position is not well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Myriad Genetics, |
RCV000410953 | SCV004018108 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-14 | 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. |
| 3DMed Clinical Laboratory Inc | RCV000677755 | SCV000803911 | uncertain significance | Gastrointestinal stromal tumor | 2017-07-25 | no assertion criteria provided | clinical testing |