Submissions for variant NM_007294.4(BRCA1):c.130del (p.Cys44fs)

dbSNP: rs80357951

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)	RCV000077485	SCV000299408	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000077485	SCV000325008	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000485954	SCV000566442	pathogenic	not provided	2015-05-05	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in BRCA1 is denoted c.130delT at the cDNA level and p.Cys44AlafsX6 (C44AfsX6) at the protein level. The normal sequence, with the base that is deleted in braces, is ATTT[T]GCAA. The deletion causes a frameshift, which changes a Cysteine to an Alanine at codon 44, and creates a premature stop codon at position 6 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496885	SCV001584921	pathogenic	Hereditary breast ovarian cancer syndrome	2023-08-17	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys44Alafs*6) 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 premature translational stop signal has been observed in individual(s) with BRCA1-related conditions (PMID: 21520333). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54194).
Baylor Genetics	RCV000077485	SCV004215012	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-08-30	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000077485	SCV000109283	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-03-28	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077485	SCV000144398	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1999-06-21	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496885	SCV000587016	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research