Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002563718 | SCV001401651 | uncertain significance | Familial adenomatous polyposis 1 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 1329 of the APC protein (p.His1329Tyr). The histidine residue is moderately 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 affected with APC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV002356982 | SCV002623170 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-20 | criteria provided, single submitter | clinical testing | The p.H1329Y variant (also known as c.3985C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 3985. The histidine at codon 1329 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is highly conserved in 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. |
All of Us Research Program, |
RCV004004829 | SCV004824637 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with tyrosine at codon 1329 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. |