Submissions for variant NM_007294.4(BRCA1):c.1009_1010del (p.Glu337fs)

dbSNP: rs1555592671

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657457	SCV000779192	pathogenic	not provided	2018-01-25	criteria provided, single submitter	clinical testing	This deletion of two nucleotides in BRCA1 is denoted c.1009_1010delGA at the cDNA level and p.Glu337LysfsX8 (E337KfsX8) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CACA[delGA]AAAAAAG. The deletion causes a frameshift which changes a Glutamic Acid to a Lysine at codon 337, and creates a premature stop codon at position 8 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.
Ambry Genetics	RCV002440402	SCV002745102	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-09	criteria provided, single submitter	clinical testing	The c.1009_1010delGA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 1009 to 1010, causing a translational frameshift with a predicted alternate stop codon (p.E337Kfs*8). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000657457	SCV004222543	likely pathogenic	not provided	2023-04-26	criteria provided, single submitter	clinical testing	This frameshift variant alters the translational reading frame of the BRCA1 mRNA and is predicted to cause the premature termination of BRCA1 protein synthesis. The variant has not been reported in individuals with BRCA1-related diseases in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Based on the available
Labcorp Genetics (formerly Invitae), Labcorp	RCV003645082	SCV004460568	pathogenic	Hereditary breast ovarian cancer syndrome	2023-05-05	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu337Lysfs*8) 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). ClinVar contains an entry for this variant (Variation ID: 545868). For these reasons, this variant has been classified as Pathogenic.