ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4391_4393delinsTT (p.Pro1464fs) (rs273900730)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164829 SCV000215512 pathogenic Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA1) RCV000031169 SCV000145081 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Color RCV000164829 SCV000905029 pathogenic Hereditary cancer-predisposing syndrome 2018-05-31 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031169 SCV000325946 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031169 SCV000300116 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000255855 SCV000321431 pathogenic not provided 2015-09-22 criteria provided, single submitter clinical testing This combined deletion and insertion is denoted BRCA1 c.4391_4393delCTAinsTT at the cDNA level and p.Pro1464LeufsX2 (P1464LfsX2) at the protein level. The normal sequence, with the bases that are deleted in braces and inserted in brackets, is TACC[CTA][TT]TAAG. The variant causes a frameshift, which changes a Proline to a Leucine at codon 1464, and creates a premature stop codon at position 2 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.4391_4393delCTAinsTT, previously reported as 4510delCTAinsTT and 4510del3insTT, has been reported in association with breast and ovarian cancer (Rostagno 2003, van der Hout 2006, Konstantopoulou 2014) and we consider this variant to be pathogenic.
GeneKor MSA RCV000239298 SCV000296774 pathogenic Familial cancer of breast 2018-08-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000048545 SCV000699141 pathogenic Hereditary breast and ovarian cancer syndrome 2016-03-03 criteria provided, single submitter clinical testing
Invitae RCV000048545 SCV000076558 pathogenic Hereditary breast and ovarian cancer syndrome 2018-02-14 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides and inserts 2 nucleotides into exon 13 of the BRCA1 mRNA (c.4391_4393delCTAinsTT). This causes a frameshift at codon 1464 which creates a premature translational stop signal (p.Pro1464Leufs*2) and is expected to result in an absent or disrupted protein product. This variant has been reported in families affected with breast and/or ovarian cancer (PMID: 12827452, 24010542, 16683254). This variant is also known as 4510del3insTT in the literature. ClinVar contains an entry for this variant (Variation ID: 37588). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031169 SCV000053769 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

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