ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4936del (p.Val1646fs) (rs80357653)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130668 SCV000185554 pathogenic Hereditary cancer-predisposing syndrome 2017-06-30 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) RCV000112428 SCV000145215 pathogenic Breast-ovarian cancer, familial 1 1999-06-21 no assertion criteria provided clinical testing
Color RCV000130668 SCV000905199 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 RCV000112428 SCV000326067 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) RCV000112428 SCV000282335 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000236929 SCV000293378 pathogenic not provided 2018-05-23 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.4936delG at the cDNA level and p.Val1646SerfsX12 (V1646SfsX12) at the protein level. The normal sequence, with the base that is deleted in braces, is AAGG[G]TCAA. The deletion causes a frameshift, which changes a Valine to a Serine at codon 1646, and creates a premature stop codon at position 12 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.4936delG, also published as 5055delG using alternate nomenclature, has been published in association with hereditary breast and ovarian cancer and has been observed in individuals of Ashkenazi Jewish descent (King 2001, Yazici 2002, Finkelman 2012, Rosenthal 2014). We consider this variant to be pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785418 SCV000923990 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000048699 SCV000076712 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1646Serfs*12) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast and/or ovarian cancer (PMID: 11710890, 25476495). This variant is also known as 5055 delG; Stop 1657 in the literature. ClinVar contains an entry for this variant (Variation ID: 55322). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048699 SCV000587434 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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