Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000490969 | SCV000579775 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-20 | criteria provided, single submitter | clinical testing | The c.729+4A>G intronic variant results from an A to G substitution 4 nucleotides after coding exon 6 in the APC gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003743752 | SCV000647707 | uncertain significance | Familial adenomatous polyposis 1 | 2018-10-20 | criteria provided, single submitter | clinical testing | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 428097). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 7 of the APC gene. It does not directly change the encoded amino acid sequence of the APC protein, but it affects a nucleotide within the consensus splice site of the intron. |