Submissions for variant NM_007294.4(BRCA1):c.2215A>T (p.Lys739Ter)

dbSNP: rs56329598

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)	RCV000111795	SCV000299724	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000111795	SCV000296411	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-12-05	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000111795	SCV000325298	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771559	SCV000904133	pathogenic	Hereditary cancer-predisposing syndrome	2023-09-06	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a 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 with a personal or family history of breast and/or ovarian cancer (PMID: 27914478, 29446198, 30078507, 31954625, 33858678). 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	RCV000771559	SCV001175528	pathogenic	Hereditary cancer-predisposing syndrome	2022-09-26	criteria provided, single submitter	clinical testing	The p.K739* pathogenic mutation (also known as c.2215A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 2215. This changes the amino acid from a lysine to a stop codon within coding exon 9. This alteration has been detected in multiple individuals with breast and/or ovarian cancer (Maistro et al. BMC Cancer 2016 12;16(1):934.; Li et al. Gynecol. Oncol. 2018 10;151(1):145-152; Rebbeck et al. Hum. Mutat. 2018 05;39(5):593-620). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496377	SCV001586756	pathogenic	Hereditary breast ovarian cancer syndrome	2024-09-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys739*) 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 ovarian cancer or undergoing testing for hereditary breast and/or ovarian cancer (PMID: 21520333, 27914478, 29446198, 30078507). ClinVar contains an entry for this variant (Variation ID: 54503). For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV000111795	SCV002512511	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2021-06-01	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 very strong, PS4 strong, PM2 moderate
All of Us Research Program, National Institutes of Health	RCV000111795	SCV004818216	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-10-23	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a 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 with a personal or family history of breast and/or ovarian cancer (PMID: 27914478, 29446198, 30078507, 31954625, 33858678). 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.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111795	SCV000144340	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	RCV000496377	SCV000587200	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research