Submissions for variant NM_007294.4(BRCA1):c.171del (p.Pro58fs)

dbSNP: rs80357660

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)	RCV000111939	SCV000299418	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	RCV000111939	SCV000325127	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000480584	SCV000572572	pathogenic	not provided	2016-12-27	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in BRCA1 is denoted c.171delG at the cDNA level and p.Pro58LeufsX11 (P58LfsX11) at the protein level. The normal sequence, with the base that is deleted in brackets, is AAGG[delG]CCTT. The deletion causes a frameshift which changes a Proline to a Leucine at codon 58, and creates a premature stop codon at position 11 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496587	SCV001200227	pathogenic	Hereditary breast ovarian cancer syndrome	2020-03-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro58Leufs*11) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 125589). This variant is not present in population databases (ExAC no frequency).
All of Us Research Program, National Institutes of Health	RCV000111939	SCV004830375	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-08-28	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 4 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 been reported in three suspected hereditary breast and ovarian cancer families (PMID: 29446198; LOVD individual #00005809, 00158946, 00161409). 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)	RCV000111939	SCV000144546	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-06-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496587	SCV000587021	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research