Submissions for variant NM_007294.4(BRCA1):c.4297del (p.Ile1432_Ile1433insTer)

dbSNP: rs2154151012

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001387981	SCV001588762	pathogenic	Hereditary breast ovarian cancer syndrome	2020-06-03	criteria provided, single submitter	clinical testing	Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ile1433*) 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.
Color Diagnostics, LLC DBA Color Health	RCV001526217	SCV001736520	likely pathogenic	Hereditary cancer-predisposing syndrome	2020-09-14	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 12 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. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been reported in an individual with breast cancer (internal data). 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 Likely Pathogenic.