Submissions for variant NM_007294.3(BRCA1):c.2199del (p.Lys734fs) (rs80357944)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077095	SCV000299715	pathogenic	Breast-ovarian cancer, familial 1	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneDx	RCV000235485	SCV000292511	pathogenic	not provided	2018-11-23	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in BRCA1 is denoted c.2199delG at the cDNA level and p.Lys734AsnfsX2 (K734NfsX2) at the protein level. The normal sequence, with the bases that are deleted in braces, is AAGA[G]AAAC. The deletion causes a frameshift, which changes a Lysine to an Asparagine at codon 734, 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. BRCA1 c.2199delG, previously reported as 2318delG, has been observed in association with pancreatic and breast cancer (Al-Sukhni 2008, Golan 2014) and is reported in the Breast Cancer Information Core (BIC) database as clinical important. We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000077095	SCV000325285	pathogenic	Breast-ovarian cancer, familial 1	2015-10-02	criteria provided, single submitter	clinical testing
Counsyl	RCV000077095	SCV000786107	pathogenic	Breast-ovarian cancer, familial 1	2018-02-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000235485	SCV000887639	pathogenic	not provided	2018-06-27	criteria provided, single submitter	clinical testing
Color	RCV000771401	SCV000903749	pathogenic	Hereditary cancer-predisposing syndrome	2018-01-22	criteria provided, single submitter	clinical testing
Invitae	RCV000496526	SCV000958701	pathogenic	Hereditary breast and ovarian cancer syndrome	2018-12-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys734Asnfs*2) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with breast cancer (PMID: 26681682, 29446198) and an individual affected with pancreatic cancer (PMID: 18762988). ClinVar contains an entry for this variant (Variation ID: 91578). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000077095	SCV000108892	pathogenic	Breast-ovarian cancer, familial 1	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077095	SCV000144332	pathogenic	Breast-ovarian cancer, familial 1	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto	RCV000496526	SCV000587198	pathogenic	Hereditary breast and ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research