ClinVar Miner

Submissions for variant NM_000038.6(APC):c.834G>A (p.Gln278=) (rs1060503261)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491926 SCV000579892 likely pathogenic Hereditary cancer-predisposing syndrome 2017-11-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Last nucleotide of exon,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Insufficient or conflicting evidence
Invitae RCV000461938 SCV000552461 likely pathogenic Familial adenomatous polyposis 1 2018-05-14 criteria provided, single submitter clinical testing This sequence change affects codon 278 of the APC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the APC protein. This variant also falls at the last nucleotide of exon 8 of the APC coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with familial adenomatous polyposis (PMID: 20223039, 23159591, Invitae). ClinVar contains an entry for this variant (Variation ID: 411344). 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. A different variant affecting this nucleotide (c.834G>C) has been determined to be pathogenic (PMID: 18433509). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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