Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000567900 | SCV000667580 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-24 | criteria provided, single submitter | clinical testing | The p.D366H variant (also known as c.1096G>C), located in coding exon 9 of the APC gene, results from a G to C substitution at nucleotide position 1096. The aspartic acid at codon 366 is replaced by histidine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with a sporadic hepatoblastoma (Aretz S et al. Pediatr Blood Cancer, 2006 Nov;47:811-8). 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. |
Color Diagnostics, |
RCV000567900 | SCV001358782 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-13 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with histidine at codon 366 of the APC protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in an individual affected with childhood onset hepatoblastoma (PMID: 16317745). This variant has been identified in 1/31392 chromosomes 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. |
Invitae | RCV003652007 | SCV002204543 | uncertain significance | Familial adenomatous polyposis 1 | 2022-12-19 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with hepatoblastoma (PMID: 16317745). This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 366 of the APC protein (p.Asp366His). ClinVar contains an entry for this variant (Variation ID: 482364). 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. |