Submissions for variant NM_007294.4(BRCA1):c.1224del (p.Lys408_Val409insTer)

dbSNP: rs879255320

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000660928	SCV000783166	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.
GeneKor MSA	RCV000239204	SCV000296791	pathogenic	not specified	2016-07-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000471171	SCV000540944	pathogenic	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
GeneDx	RCV000520798	SCV000618032	pathogenic	not provided	2023-11-08	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 1343del; This variant is associated with the following publications: (PMID: 24249303, 26187060, 31368036, 29176636, 33067490, 20104584, 34296289)
Invitae	RCV000793345	SCV000932693	pathogenic	Hereditary breast ovarian cancer syndrome	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val409*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 24249303). This variant is also known as 1343delA. ClinVar contains an entry for this variant (Variation ID: 252436). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV001189627	SCV001356945	pathogenic	Hereditary cancer-predisposing syndrome	2020-04-28	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with breast and/or ovarian cancer (PMID: 24249303, 26187060). 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.
AiLife Diagnostics, AiLife Diagnostics	RCV000520798	SCV002502358	pathogenic	not provided	2022-02-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001189627	SCV002659245	pathogenic	Hereditary cancer-predisposing syndrome	2022-01-11	criteria provided, single submitter	clinical testing	The c.1224delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1224, causing a translational frameshift with a predicted alternate stop codon (p.V409*). This alteration has been identified in multiple individuals diagnosed with breast and/or ovarian cancer (Arai M et al. J Hum Genet, 2018 Apr;63:447-457; Bernstein-Molho R et al. Breast Cancer Res Treat, 2019 Nov;178:231-237). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000660928	SCV003927210	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-05-05	no assertion criteria provided	clinical testing	A pathogenic mutation was detected in the BRCA1 gene (p.Val409fs). This mutation causes a frameshift.