Submissions for variant NM_007294.4(BRCA1):c.2594del (p.Lys865fs)

dbSNP: rs80357756

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)	RCV000077523	SCV000299791	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	RCV000047891	SCV000075904	pathogenic	Hereditary breast ovarian cancer syndrome	2015-09-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Truncating variants in BRCA1 are known to be pathogenic. This particular truncation has been reported in identical twins, both with ovarian cancer (PMID: 9406579). This variant is also known as 2711delA in the literature. This sequence change deletes 1 nucleotide from exon 10 of the BRCA1 mRNA (c.2594delA), causing a frameshift at codon 865. This creates a premature translational stop signal (p.Lys865Serfs*28) and is expected to result in an absent or disrupted protein product.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000505972	SCV000602722	pathogenic	not specified	2017-01-25	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000578073	SCV000679702	pathogenic	Hereditary cancer-predisposing syndrome	2017-07-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002477167	SCV002793448	pathogenic	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S	2021-12-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000578073	SCV004360266	pathogenic	Hereditary cancer-predisposing syndrome	2023-06-26	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 10 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 two siblings both affected with ovarian cancer (PMID: 9406579). 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.
Ambry Genetics	RCV000578073	SCV005025766	pathogenic	Hereditary cancer-predisposing syndrome	2023-12-14	criteria provided, single submitter	clinical testing	The c.2594delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2594, causing a translational frameshift with a predicted alternate stop codon (p.K865Sfs*28). This alteration has been identified in families with history of breast and ovarian cancers (Miesfeldt S et al. Cancer Genet Cytogenet, 1998 Jan;100:43-8). (Flaum N et al. Genet Med, 2022 Dec;24:2578-2586). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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.
Sharing Clinical Reports Project (SCRP)	RCV000077523	SCV000109324	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2007-09-24	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077523	SCV000144485	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1999-04-06	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000047891	SCV000587234	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research