ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4182_4183dup (p.Gln1395fs)

dbSNP: rs80357742
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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) RCV000143835 SCV000300088 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.
Ambry Genetics RCV000221513 SCV000278475 pathogenic Hereditary cancer-predisposing syndrome 2022-06-19 criteria provided, single submitter clinical testing The c.4182_4183dupTC pathogenic mutation, located in coding exon 10 of the BRCA1 gene, results from a duplication of 2 nucleotides at positions 4182 and 4183, causing a translational frameshift with a predicted alternate stop codon (p.Q1395Lfs*11). 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.
GeneDx RCV000235957 SCV000292521 pathogenic not provided 2015-11-12 criteria provided, single submitter clinical testing This duplication of 2 nucleotides in BRCA1 is denoted c.4182_4183dupTC at the cDNA level and p.Gln1395LeufsX11 (Q1395LfsX11) at the protein level. The normal sequence, with the bases that are duplicated in braces, is CCAC[TC]AGgt, where the capital letters are exonic and lowercase are intronic. The duplication causes a frameshift, which changes a Glutamine to a Leucine at codon 1395, and creates a premature stop codon at position 11 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.4182_4183dupTC, also reported as BRCA1 Q1395fs, has been observed in at least one woman with serous ovarian cancer (Yang 2011). We consider this variant to be pathogenic.
Invitae RCV001383016 SCV001582024 pathogenic Hereditary breast ovarian cancer syndrome 2023-06-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55124). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 21990299). This variant is present in population databases (rs80357742, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln1395Leufs*11) 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).
Sharing Clinical Reports Project (SCRP) RCV000143835 SCV000115121 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2012-03-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000143835 SCV000145006 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2004-11-25 no assertion criteria provided clinical testing

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