ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2209del (p.Thr737fs)

dbSNP: rs1060502333
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Total submissions: 5
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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) RCV000661163 SCV000783417 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.
Invitae RCV000461584 SCV000549290 pathogenic Hereditary breast ovarian cancer syndrome 2016-06-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 737 (p.Thr737Glnfs*16) of the BRCA1 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000657471 SCV000779206 pathogenic not provided 2018-02-15 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.2209delA at the cDNA level and p.Thr737GlnfsX16 (T737QfsX16) at the protein level. The normal sequence, with the base that is deleted in brackets, is AGAA[delA]CAGT. The deletion causes a frameshift which changes a Threonine to a Glutamine at codon 737, and creates a premature stop codon at position 16 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 RCV001014792 SCV001175548 pathogenic Hereditary cancer-predisposing syndrome 2018-04-18 criteria provided, single submitter clinical testing The c.2209delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2209, causing a translational frameshift with a predicted alternate stop codon (p.T737Qfs*16). 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.
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne RCV000785385 SCV000923956 pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research

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