Submissions for variant NM_007294.4(BRCA1):c.1252del (p.Glu418fs)

dbSNP: rs876660623

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000661274	SCV000783539	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2017-12-15	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics	RCV000218101	SCV000278199	pathogenic	Hereditary cancer-predisposing syndrome	2022-08-01	criteria provided, single submitter	clinical testing	The c.1252delG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1252, causing a translational frameshift with a predicted alternate stop codon (p.E418Rfs*2). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
GeneDx	RCV000484830	SCV000566559	pathogenic	not provided	2015-05-07	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in BRCA1 is denoted c.1252delG at the cDNA level and p.Glu418ArgfsX2 (E418RfsX2) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 1371delG. The normal sequence, with the base that is deleted in braces, is AAAT[G]AGGT. The deletion causes a frameshift, which changes a Glutamic Acid to an Arginine at codon 418, and creates a premature stop codon at position 2 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.