Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003534624 | SCV000822638 | uncertain significance | Familial adenomatous polyposis 1 | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 96 of the APC protein (p.Tyr96Phe). 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: 572748). 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. |
Ambry Genetics | RCV001016872 | SCV001177873 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-18 | criteria provided, single submitter | clinical testing | The c.287A>T (p.Y96F) alteration is located in exon 4 (coding exon 3) of the APC gene. This alteration results from a A to T substitution at nucleotide position 287, causing the tyrosine (Y) at amino acid position 96 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV001016872 | SCV004359242 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-13 | criteria provided, single submitter | clinical testing | This missense variant replaces tyrosine with phenylalanine at codon 96 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 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. |