Submissions for variant NM_000038.6(APC):c.1548+1G>C

dbSNP: rs1114167599

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000491069	SCV000579930	pathogenic	Hereditary cancer-predisposing syndrome	2016-10-27	criteria provided, single submitter	clinical testing	The c.1548+1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide after coding exon 11 of the APC gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Another alteration affecting this same nucleotide, c.1548+1G>T (also designated as IVS11+1G>T in published literature), has been reported in an FAP family from the Czech Republic, and functional studies have shown that it leads to aberrant splicing with two separate truncated protein transcripts observed: one with skipping of exon 11 and one which included both exon 11 and intron 11 (Schwarzová L et al. Fam. Cancer. 2013 Mar;12(1):35-42; Kohoutová M et al. Hum. Mutat. 2002 Apr;19(4):460-1). 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. As such, this alteration is classified as pathogenic.
Eurofins Ntd Llc (ga)	RCV000596811	SCV000702958	pathogenic	not provided	2016-10-27	criteria provided, single submitter	clinical testing