Submissions for variant NM_007294.4(BRCA1):c.3354G>T (p.Gln1118His)

dbSNP: rs80357334

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000048160	SCV000076173	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-07-12	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 37525). This missense change has been observed in individual(s) with Breast Cancer Information Core database (PMID: 10923033). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 1118 of the BRCA1 protein (p.Gln1118His).
Ambry Genetics	RCV000164761	SCV000215437	uncertain significance	Hereditary cancer-predisposing syndrome	2020-01-24	criteria provided, single submitter	clinical testing	The p.Q1118H variant (also known as c.3354G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3354. The glutamine at codon 1118 is replaced by histidine, an amino acid with highly similar properties. 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.
Counsyl	RCV000031106	SCV000488151	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2016-01-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586936	SCV000699024	uncertain significance	not provided	2016-10-13	criteria provided, single submitter	clinical testing	Variant summary: The BRCA1 c.3354G>T (p.Gln1118His) variant involves the alteration of a non-conserved nucleotide. This variant is not located in any known domain (InterPro). 2/4 in silico tools predict a benign outcome for this variant. This variant is absent from 121140 control chromosomes from ExAC. The variant has been reported to co-occur with a known deleterious variant BRCA1 p.W1508X (BIC). Co-occurrence with the same pathogenic variant was noted in an internal sample undergoing genetic testing. This data strongly supports a benign outcome of Q1118H. Multiple clinical diagnostic laboratories have classified this variant as uncertain significance without evidence to independently evaluate. Taken together, this variant is classified as VUS-possibly benign variant based on two independent records of co-occurrence with the same pathgenic variant.
University of Washington Department of Laboratory Medicine, University of Washington	RCV000164761	SCV003852099	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).
Sharing Clinical Reports Project (SCRP)	RCV000031106	SCV000053702	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2012-04-18	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031106	SCV000144734	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2003-12-23	no assertion criteria provided	clinical testing