Submissions for variant NM_007294.4(BRCA1):c.112_113del (p.Lys38fs)

dbSNP: rs80357949

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)	RCV000111790	SCV000299405	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000047355	SCV000075368	pathogenic	Hereditary breast ovarian cancer syndrome	2023-12-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys38Valfs*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 breast and/or ovarian cancer (PMID: 8533757, 9145677, 11844822, 14760071, 21080930). This variant is also known as c.230delAA and c.231delAA. ClinVar contains an entry for this variant (Variation ID: 54141). For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000111790	SCV000324959	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000574475	SCV000660935	pathogenic	Hereditary cancer-predisposing syndrome	2021-01-06	criteria provided, single submitter	clinical testing	The c.112_113delAA pathogenic mutation, located in coding exon 2 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 112 to 113, causing a translational frameshift with a predicted alternate stop codon (p.K38Vfs*2). This mutation has been reported in multiple HBOC families (Friedman LS et al. Am. J. Hum. Genet. 1995 Dec;57:1284-97; Couch FJ et al. N. Engl. J. Med. 1997 May;336:1409-15; Shih HA et al. J. Clin. Oncol. 2002 Feb;20:994-9). Of note, this mutation may be referred to as 230delAA or 231delAA in some literature. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759488	SCV000888833	pathogenic	not provided	2018-07-10	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000111790	SCV004216862	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-12-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000574475	SCV004361136	pathogenic	Hereditary cancer-predisposing syndrome	2022-04-05	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 3 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals and families affected with breast and/or ovarian cancer (PMID: 8533757, 9145677, 11844822, 14760071, 21080930), and has been identified in 4 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV000759488	SCV005413240	pathogenic	not provided	2023-10-11	criteria provided, single submitter	clinical testing	PM2, PM5_strong, PVS1
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111790	SCV000144333	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000047355	SCV000587011	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research