Submissions for variant NM_007294.4(BRCA1):c.4113del (p.Cys1372fs)

dbSNP: rs80357861

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112262	SCV000282323	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-04-22	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112262	SCV000325852	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV000551100	SCV000635943	pathogenic	Hereditary breast ovarian cancer syndrome	2023-03-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Cys1372Valfs*21) 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: 10464631, 26014432). This variant is also known as c.4232delG. ClinVar contains an entry for this variant (Variation ID: 125680). For these reasons, this variant has been classified as Pathogenic.
Counsyl	RCV000112262	SCV000677651	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-11-28	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000585711	SCV000693532	pathogenic	not provided	2020-01-01	criteria provided, single submitter	clinical testing	This sequence change deletes one nucleotide from exon 12 of the BRCA1 mRNA (c.4113delG), causing a frameshift after codon 1372 and the creation of a premature translational stop signal 21 amino acid residues later (p.Cys1372Valfs*21). This is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. The mutation database ClinVar contains entries for this variant (Variation ID: 125680).
GeneDx	RCV000585711	SCV000779102	pathogenic	not provided	2017-08-10	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in BRCA1 is denoted c.4113delG at the cDNA level and p.Cys1372ValfsX21 (C1372VfsX21) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTGG[delG]TGTG. The deletion causes a frameshift which changes a Cysteine to a Valine at codon 1372, and creates a premature stop codon at position 21 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.4113delG, previously reported as 4232delG using alternate nomenclature, has been seen in at least one individual undergoing clinical BRCA1/2 testing due to personal and/or family history of cancer (Judkins 2005). We consider this variant to be pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000776209	SCV000911362	pathogenic	Hereditary cancer-predisposing syndrome	2020-03-12	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 11 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 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	RCV000776209	SCV001183566	pathogenic	Hereditary cancer-predisposing syndrome	2021-07-27	criteria provided, single submitter	clinical testing	The c.4113delG pathogenic mutation, located in coding exon 10 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 4113, causing a translational frameshift with a predicted alternate stop codon. This mutation has been previously reported in one Australian breast and/or ovarian cancer family (Rebbeck TR et al. Hum. Mutat. 2018 May;39(5):593-620). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function due to an abnormal transcript, a translational frameshift leading to premature truncation, or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Baylor Genetics	RCV000112262	SCV004216825	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-02-21	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112262	SCV000144984	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing
Institute of Human Genetics, Medical University Innsbruck	RCV000112262	SCV000212001	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-02-11	no assertion criteria provided	clinical testing