Submissions for variant NM_007294.4(BRCA1):c.3365_3366del (p.Thr1122fs)

dbSNP: rs80357892

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112081	SCV000299934	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics	RCV000162863	SCV000213350	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-10	criteria provided, single submitter	clinical testing	The c.3365_3366delCA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 3365 to 3366, causing a translational frameshift with a predicted alternate stop codon (p.T1122Rfs*10). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112081	SCV000325635	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759517	SCV000888886	pathogenic	not provided	2015-12-30	criteria provided, single submitter	clinical testing
Invitae	RCV000496347	SCV001586301	pathogenic	Hereditary breast ovarian cancer syndrome	2023-01-31	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54859). This variant is also known as 3484delCA. This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 27469594). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr1122Argfs*10) 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)	RCV000112081	SCV000144741	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496347	SCV000587306	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research