Submissions for variant NM_007294.4(BRCA1):c.4186C>T (p.Gln1396Ter)

dbSNP: rs80357011

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112291	SCV000783164	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2017-12-15	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112291	SCV000325890	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Oslo University Hospital	RCV000112291	SCV000564340	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-07-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759534	SCV000888908	pathogenic	not provided	2017-11-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001022003	SCV001183690	pathogenic	Hereditary cancer-predisposing syndrome	2019-03-18	criteria provided, single submitter	clinical testing	The p.Q1396* pathogenic mutation (also known as c.4186C>T), located in coding exon 11 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4186. This changes the amino acid from a glutamine to a stop codon within coding exon 11. In a large, clinic-based BRCA1/2 testing cohort in Norway, this mutation was detected in 1 family (Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3). This mutation was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). In another study, this mutation was detected in 1/774 women with triple-negative breast cancer, and the patient who carried this mutation also carried a BRCA2 mutation (Wong-Brown MW et al. Breast Cancer Res. Treat., 2015 Feb;150:71-80). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae	RCV000496729	SCV001590148	pathogenic	Hereditary breast ovarian cancer syndrome	2022-04-04	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55135). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 12585668, 25682074). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1396*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584).
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112291	SCV000145023	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1999-06-22	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496729	SCV000587382	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
BRCAlab, Lund University	RCV000112291	SCV002588808	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-08-26	no assertion criteria provided	clinical testing