Submissions for variant NM_007294.4(BRCA1):c.4391_4393delinsTT (p.Pro1464fs)

dbSNP: rs273900730

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031169	SCV000300116	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	RCV000048545	SCV000076558	pathogenic	Hereditary breast ovarian cancer syndrome	2025-01-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro1464Leufs*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). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 12827452, 16683254, 24010542, 31209999). This variant is also known as 4510del3insTT. ClinVar contains an entry for this variant (Variation ID: 37588). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000164829	SCV000215512	pathogenic	Hereditary cancer-predisposing syndrome	2022-08-19	criteria provided, single submitter	clinical testing	The c.4391_4393delCTAinsTT pathogenic mutation, located in coding exon 12 of the BRCA1 gene, results from the deletion of 3 nucleotides and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon (p.P1464Lfs*2). This mutation has been previously reported in breast/ovarian cancer families (Rostagno P et al. J. Hum. Genet. 2003; 48(7):362-6; Konstantopoulou I, Clin. Genet. 2014 Jan; 85(1):36-42). Of note, this alteration is also referred to as 4510delCTAinsTT in published literature. In addition to the information available 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.
GeneKor MSA	RCV000239298	SCV000296774	pathogenic	Familial cancer of breast	2020-01-01	criteria provided, single submitter	clinical testing	This sequence change deletes 3 nucleotides and inserts 2 nucleotides into exon 14 of the BRCA1 mRNA (c.4391_4393delCTAinsTT) causing a frameshift after codon 1464 and the creation of a premature translation stop signal 2 amino acid residues later p.(Pro1464Leufs) This is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particularly variant has been described in families affected with breast and/or ovarian cancer (PMID: 12827452, 24010542). This mutation has been described in the mutation database ClinVar (Variation ID: 37588).
GeneDx	RCV000255855	SCV000321431	pathogenic	not provided	2023-06-29	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Identified in individuals with personal or family history of breast and/or ovarian cancer (Rostagno et al., 2003; van der Hout et al., 2006; Konstantopoulou et al., 2014; Sunar et al., 2022); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 4510delCTAinsTT and 4510del3insTT; This variant is associated with the following publications: (PMID: 12827452, 10952777, 24010542, 26300996, 11748305, 16683254, 31159747, 31209999, 16267036, 33629534)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000031169	SCV000325946	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000048545	SCV000699141	pathogenic	Hereditary breast ovarian cancer syndrome	2016-03-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164829	SCV000905029	pathogenic	Hereditary cancer-predisposing syndrome	2020-11-16	criteria provided, single submitter	clinical testing	This variant replaces three nucleotides in exon 13 of the BRCA1 gene with two new nucleotides, 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 affected with or at risk for breast and ovarian cancer (PMID: 12827452, 16267036, 24010542, 29310832, 30430080, 31209999). 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.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000255855	SCV001450018	pathogenic	not provided	2018-07-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000255855	SCV002563412	pathogenic	not provided	2019-04-01	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000255855	SCV005198206	pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005357176	SCV005914233	pathogenic	Fanconi anemia, complementation group S	2024-06-17	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031169	SCV000053769	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031169	SCV000145081	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing