Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001189493 | SCV001356801 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-30 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003770134 | SCV001492991 | uncertain significance | Familial adenomatous polyposis 1 | 2020-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 392 of the APC protein (p.His392Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 926694). 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 C15"). 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 | RCV001189493 | SCV002631268 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-12-23 | criteria provided, single submitter | clinical testing | The p.H392Y variant (also known as c.1174C>T), located in coding exon 9 of the APC gene, results from a C to T substitution at nucleotide position 1174. The histidine at codon 392 is replaced by tyrosine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 70000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.H392Y remains unclear. |