Submissions for variant NM_007294.4(BRCA1):c.3347T>G (p.Val1116Gly)

dbSNP: rs786203153

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166338	SCV000217124	uncertain significance	Hereditary cancer-predisposing syndrome	2014-10-13	criteria provided, single submitter	clinical testing	The p.V1116G variant (also known as c.3347T>G or 3466T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 3347. The valine at codon 1116 is replaced by glycine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 64,000 alleles tested) in our clinical cohort. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be benign and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.V1116G remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington	RCV000166338	SCV003852132	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).