Submissions for variant NM_000038.6(APC):c.346G>T (p.Gly116Cys)

dbSNP: rs142637152

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481675	SCV000567254	uncertain significance	not provided	2015-07-14	criteria provided, single submitter	clinical testing	This variant is denoted APC c.346G>T at the cDNA level, p.Gly116Cys (G116C) at the protein level, and results in the change of a Glycine to a Cysteine (GGT>TGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Gly116Cys was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Glycine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Gly116Cys occurs at a position that is conserved across species and is not located in a known functional domain (Azzopardi 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether APC Gly116Cys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV002455917	SCV002613935	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-16	criteria provided, single submitter	clinical testing	The p.G116C variant (also known as c.346G>T), located in coding exon 3 of the APC gene, results from a G to T substitution at nucleotide position 346. The glycine at codon 116 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.