Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000573972 | SCV000675929 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-02-17 | criteria provided, single submitter | clinical testing | The p.C607S variant (also known as c.1820G>C), located in coding exon 14 of the APC gene, results from a G to C substitution at nucleotide position 1820. The cysteine at codon 607 is replaced by serine, an amino acid with dissimilar 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. |
Color Diagnostics, |
RCV000573972 | SCV000686861 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-12 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with serine at codon 607 of the APC protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer 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. |
Invitae | RCV001853812 | SCV002148351 | uncertain significance | Familial adenomatous polyposis 1 | 2021-09-29 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with serine at codon 607 of the APC protein (p.Cys607Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. 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. ClinVar contains an entry for this variant (Variation ID: 486778). 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 disruptive. 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. |
Foundation for Research in Genetics and Endocrinology, |
RCV002463453 | SCV002600891 | uncertain significance | Desmoid disease, hereditary | 2022-09-13 | criteria provided, single submitter | clinical testing | A heterozygous missense variation in exon 15 of the APC gene that results in the amino acid substitution of Serine for Cysteine at codon 607 was detected. The observed variation has not been reported in the 1000 genomes and gnomAD databases. The in silico predictions of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. |