Submissions for variant NM_007294.4(BRCA1):c.2728C>G (p.Gln910Glu)

dbSNP: rs397509004

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000637654	SCV000759123	likely benign	Hereditary breast ovarian cancer syndrome	2022-02-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002458025	SCV002738693	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-27	criteria provided, single submitter	clinical testing	The p.Q910E variant (also known as c.2728C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2728. The glutamine at codon 910 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration was not observed in 53 unselected male breast cancer patients and was observed with an allele frequency of 0.0001 in 12,490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington	RCV002458025	SCV003849398	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).