ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3285del (p.Lys1095fs) (rs397509051)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000169309 SCV000299907 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Counsyl RCV000169309 SCV000220631 likely pathogenic Breast-ovarian cancer, familial 1 2014-08-25 criteria provided, single submitter literature only
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000169309 SCV000325598 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000478254 SCV000568415 pathogenic not provided 2016-08-03 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.3285delA at the cDNA level and p.Lys1095AsnfsX14 (K1095NfsX14) at the protein level. The normal sequence, with the base that is deleted in brackets, is ATAA[delA]CAAA. The deletion causes a frameshift which changes a Lysine to an Asparagine at codon 1095, and creates a premature stop codon at position 14 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.3285delA, previously published as 3404delA using alternate nomenclature, has been reported in association with Hereditary Breast and Ovarian Cancer (Papi 2009, Caux-Moncoutier 2011). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000478254 SCV000600324 pathogenic not provided 2016-11-20 criteria provided, single submitter clinical testing
Color Health, Inc RCV000775160 SCV000909310 pathogenic Hereditary cancer-predisposing syndrome 2020-12-30 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 10 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, functional studies have not been reported for this variant. This variant has been observed in individuals and families affected with breast and ovarian cancer (PMID: 18821011, 21120943, 30263092, 31336956, 32438681; Color internal data). This variant also is reported as a suspected founder mutation in Italy (PMID: 18821011, 23199084). 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.
Ambry Genetics RCV000775160 SCV001181053 pathogenic Hereditary cancer-predisposing syndrome 2019-01-30 criteria provided, single submitter clinical testing The c.3285delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 3285, causing a translational frameshift with a predicted alternate stop codon (p.K1095Nfs*14). This mutation has been previously described in three unrelated Tuscan hereditary breast and ovarian cancer (HBOC) syndrome families (Papi L et al. Breast Cancer Res. Treat. 2009 Oct;117:497-504). 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.

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