Submissions for variant NM_007294.4(BRCA1):c.1039_1040del (p.Leu347fs)

dbSNP: rs397508827

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000257358	SCV000323267	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-10-18	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneDx	RCV000235412	SCV000293473	pathogenic	not provided	2016-02-01	criteria provided, single submitter	clinical testing	This deletion of 2 nucleotides in BRCA1 is denoted c.1039_1040delCT at the cDNA level and p.Leu347ValfsX2 (L347VfsX2) at the protein level. The normal sequence, with the bases that are deleted in braces, is TCCC[CT]GTGT. The deletion causes a frameshift, which changes a Leucine to a Valine at codon 347, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as BRCA1 c.1158_1159delCT and published as BRCA1 1158delCT using alternate nomenclature, has been reported in families with breast and/or ovarian cancer (Meindl 2002, Song 2014). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000257358	SCV000324934	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000235412	SCV001470150	pathogenic	not provided	2019-10-04	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001386876	SCV001587269	pathogenic	Hereditary breast ovarian cancer syndrome	2024-07-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu347Valfs*2) 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 clinical features of hereditary breast and ovarian cancer syndrome (PMID: 11802209, 28828701, 29176636, 29907814, 31209999). This variant is also known as c.1158delCT. ClinVar contains an entry for this variant (Variation ID: 54105). For these reasons, this variant has been classified as Pathogenic.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000257358	SCV002546228	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1		criteria provided, single submitter	clinical testing