Submissions for variant NM_007294.4(BRCA1):c.2158G>T (p.Glu720Ter)

dbSNP: rs80356875

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)	RCV000031034	SCV000299709	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.
Ambry Genetics	RCV000162852	SCV000213339	pathogenic	Hereditary cancer-predisposing syndrome	2024-08-06	criteria provided, single submitter	clinical testing	The p.E720* pathogenic mutation (also known as c.2158G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 2158. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This mutation has been identified in multiple individuals with a personal and/or family history of breast and/or ovarian cancer (Tworek H et al. Cancer Genet. Cytogenet. 1999 Jul;112:105-18; Laitman Y et al. Breast Cancer Res. Treat. 2011 Jun;127:489-95; El Saghir NS et al. Oncologist. 2015 Apr;20:357-64). 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000031034	SCV000325272	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000585721	SCV000693515	pathogenic	not provided	2020-01-01	criteria provided, single submitter	clinical testing	This variant is a single amino acid change from Glutamic Acid to a Termination codon at amino acid residue 720 of the BRCA1 gene. It is expected to result in a truncated, non-functional protein. Truncating variants in the BRCA1 gene are known to be pathogenic. The mutation database ClinVar contains entries for this variant (Variation ID: 37453).
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000585721	SCV000887637	pathogenic	not provided	2017-09-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001386504	SCV001586758	pathogenic	Hereditary breast ovarian cancer syndrome	2022-05-16	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 37453). This sequence change creates a premature translational stop signal (p.Glu720*) 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: 10686936, 25777348, 26187060, 29446198). For these reasons, this variant has been classified as Pathogenic.
Department of Human Genetics, Hannover Medical School	RCV000031034	SCV005367953	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2024-10-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162852	SCV006061516	pathogenic	Hereditary cancer-predisposing syndrome	2023-05-26	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 several individuals affected with breast and/or ovarian cancer (PMID: 10686936, 20960228, 25777348, 30287823) and has been identified in two 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.
Sharing Clinical Reports Project (SCRP)	RCV000031034	SCV000053628	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2010-07-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031034	SCV000144315	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1998-04-15	no assertion criteria provided	clinical testing