Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003535998 | SCV000950969 | uncertain significance | Familial adenomatous polyposis 1 | 2023-03-31 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. 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. ClinVar contains an entry for this variant (Variation ID: 654727). This variant has not been reported in the literature in individuals affected with APC-related conditions. This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 436 of the APC protein (p.Asn436Tyr). |
Ambry Genetics | RCV002381800 | SCV002689953 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-04 | criteria provided, single submitter | clinical testing | The p.N436Y variant (also known as c.1306A>T), located in coding exon 9 of the APC gene, results from an A to T substitution at nucleotide position 1306. The asparagine at codon 436 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |