Submissions for variant NM_007294.4(BRCA1):c.3351dup (p.Gln1118fs)

dbSNP: rs80357785

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112077	SCV000299928	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000112077	SCV000296483	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-06-07	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112077	SCV000325627	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Counsyl	RCV000112077	SCV000488690	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-05-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589888	SCV000699023	pathogenic	Hereditary breast ovarian cancer syndrome	2016-05-11	criteria provided, single submitter	clinical testing	Variant summary: The BRCA1 c.3351dupT (p.Gln1118Serfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.3358_3359delGT (p.Val1120fs), c.3365_3366delCA (p.Thr1122fs) and 3400G>T (p.Glu1134X)). This variant is absent in 121140 control chromosomes. In addition, a reputable database classified this variant as Pathogenic. Taken together, this variant is classified as Pathogenic.
Invitae	RCV000589888	SCV000937532	pathogenic	Hereditary breast ovarian cancer syndrome	2023-12-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1118Serfs*4) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 23096105, 27062684, 29446198). This variant is also known as 3470insT. ClinVar contains an entry for this variant (Variation ID: 125630). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002321586	SCV002607151	pathogenic	Hereditary cancer-predisposing syndrome	2016-07-13	criteria provided, single submitter	clinical testing	The c.3351dupT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of T at nucleotide position 3351, causing a translational frameshift with a predicted alternate stop codon. This alteration, also referred to as 3470insT in the literature, has been reported in an Italian woman who was diagnosed with breast cancer at age 23 (Vietri MT et al. Clin. Chem. Lab. Med. 2012 Dec;50(12):2171-80). 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.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112077	SCV000144733	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing