Submissions for variant NM_007294.4(BRCA1):c.2710G>C (p.Glu904Gln)

dbSNP: rs80357035

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130465	SCV000185330	uncertain significance	Hereditary cancer-predisposing syndrome	2013-10-15	criteria provided, single submitter	clinical testing	​The p.E904Q variant (also known as c.2710G>C or 2829G>C) is located in coding exon 9 of the BRCA1 gene. This alteration results from a G to C substitution at nucleotide position 2710. The glutamic acid at codon 904 is replaced by glutamine, an amino acid with highly similar 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. Based on protein sequence alignment, this amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging by PolyPhen but tolerated by SIFT in silico analyses. Since supporting evidence is limited at this time, the clinical significance of p.E904Q remains unclear.
Invitae	RCV000229677	SCV000289764	uncertain significance	Hereditary breast ovarian cancer syndrome	2016-03-27	criteria provided, single submitter	clinical testing	In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (rs80357035, ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 141808). This sequence change replaces glutamic acid with glutamine at codon 904 of the BRCA1 protein (p.Glu904Gln). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and glutamine.
Color Diagnostics, LLC DBA Color Health	RCV000130465	SCV000537567	uncertain significance	Hereditary cancer-predisposing syndrome	2019-03-27	criteria provided, single submitter	clinical testing
University of Washington Department of Laboratory Medicine, University of Washington	RCV000130465	SCV003849408	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).