ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1695dup (p.Lys566fs)

dbSNP: rs273897664
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Total submissions: 6
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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) RCV000111665 SCV000299635 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000111665 SCV000296297 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-03-02 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000111665 SCV000564295 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-07-01 criteria provided, single submitter clinical testing
GeneDx RCV000483200 SCV000564721 pathogenic not provided 2015-01-30 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA1 is denoted c.1695dupG at the cDNA level and p.Lys566GlufsX4 (K566EfsX4) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ATGA[G]AAAAAT. The duplication causes a frameshift, which changes a Lysine to a Glutamic Acid at codon 566, and creates a premature stop codon at position 4 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.1695dupG, previously reported as 1814dupG, has been reported in the Breast Cancer Information Core (BIC) database as being clinically significant. we consider this variant to be pathogenic.
Ambry Genetics RCV003372616 SCV004093326 pathogenic Hereditary cancer-predisposing syndrome 2023-08-08 criteria provided, single submitter clinical testing The c.1695dupG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of G at nucleotide position 1695, causing a translational frameshift with a predicted alternate stop codon (p.K566Efs*4). This alteration has been reported in breast and/or ovarian cancer patients (Kluska A et al. BMC Med Genomics, 2015 May;8:19; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Arvai KJ et al. Hered Cancer Clin Pract, 2019 Jul;17:19). 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111665 SCV000144158 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2005-07-21 no assertion criteria provided clinical testing

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