Submissions for variant NM_007294.4(BRCA1):c.5419del (p.Ile1807fs)

dbSNP: rs80357934

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112649	SCV000300257	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112649	SCV000326309	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Genologica Medica	RCV000112649	SCV000577940	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2017-01-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001185951	SCV001352267	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 22 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	RCV001185951	SCV002653997	pathogenic	Hereditary cancer-predisposing syndrome	2017-03-14	criteria provided, single submitter	clinical testing	The c.5419delA pathogenic mutation, located in coding exon 21 of the BRCA1 gene, results from a deletion of one nucleotide at position 5419, causing a translational frameshift within the functionally-important BRCT2 domain and a predicted alternate stop codon. This mutation (designated as 5537delA) was identified and shown to segregate with disease in a Spanish hereditary breast/ovarian cancer family (Díez O et al. Int. J. Cancer 1999 Nov;83(4):465-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112649	SCV000145507	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496272	SCV000587506	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research