Submissions for variant NM_007294.4(BRCA1):c.4146_4155dup (p.Ser1386fs)

dbSNP: rs483353079

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)	RCV000256584	SCV000323732	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000256584	SCV000325865	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Oslo University Hospital	RCV000256584	SCV000564381	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-02-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000481226	SCV000566083	pathogenic	not provided	2023-09-22	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in a Norwegian family, cancer history not provided (Heramb et al., 2018); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 4265_4274dup10; This variant is associated with the following publications: (PMID: 34981296, 29339979)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000481226	SCV000887688	pathogenic	not provided	2017-09-21	criteria provided, single submitter	clinical testing
Invitae	RCV001036124	SCV001199474	pathogenic	Hereditary breast ovarian cancer syndrome	2023-11-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1386Leufs*8) 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 hereditary breast and/or ovarian cancer (PMID: 29339979). ClinVar contains an entry for this variant (Variation ID: 266452). For these reasons, this variant has been classified as Pathogenic.