Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000475761 | SCV000552506 | uncertain significance | Familial adenomatous polyposis 1 | 2024-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1915 of the APC protein (p.Lys1915Glu). This variant is not present in population databases (gnomAD no frequency). 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: 133511). 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 | RCV000475761 | SCV000784945 | uncertain significance | Familial adenomatous polyposis 1 | 2017-02-14 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002345425 | SCV002649693 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-13 | criteria provided, single submitter | clinical testing | The p.K1915E variant (also known as c.5743A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 5743. The lysine at codon 1915 is replaced by glutamic acid, an amino acid with similar properties. This variant was identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS ONE. 2014 Apr;9:e94554). This amino acid position is highly conserved through mammals but not in all 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, |
RCV000475761 | SCV004018819 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-22 | 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 | RCV000120017 | SCV000084147 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |