Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001021331 | SCV001182934 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-18 | criteria provided, single submitter | clinical testing | The c.3873+1G>C intronic variant results from a G to C substitution one nucleotide after coding exon 26 of the SMARCA4 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, the exact functional impact of the predicted in-frame protein loss is unknown as this region of the SMARCA4 gene is excluded from other biologically relevant transcripts (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |