ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4611_4612insG (p.Gln1538fs) (rs80357915)

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Total submissions: 8
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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) RCV000112364 SCV000300144 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048605 SCV000076618 pathogenic Hereditary breast and ovarian cancer syndrome 2015-02-20 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 14 of the BRCA1 mRNA (c.4611_4612insG), causing a frameshift at codon 1538. This creates a premature translational stop signal (p.Gln1538Alafs*36) and is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particular truncation has been reported in multiple individuals with breast cancer (PMID: 20838878). In the literature, this variant is also known as 4730insG. ClinVar contains entries for this variant (RCV000112364, RCV000131883). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131883 SCV000186938 pathogenic Hereditary cancer-predisposing syndrome 2016-03-23 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000112364 SCV000296485 pathogenic Breast-ovarian cancer, familial 1 2016-06-03 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112364 SCV000326008 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000657506 SCV000779241 pathogenic not provided 2018-04-16 criteria provided, single submitter clinical testing This insertion of one nucleotide in BRCA1 is denoted c.4611_4612insG at the cDNA level and p.Gln1538AlafsX36 (Q1538AfsX36) at the protein level. The normal sequence, with the base that is inserted in brackets, is GCAA[insG]CAGC. The insertion causes a frameshift which changes a Glutamine to an Alanine at codon 1538, and creates a premature stop codon at position 36 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.4611_4612insG, also known as c.4730_4731insG by alternate nomenclature, has been identified in several individuals with breast cancer (Donenberg 2011). We consider this variant to be pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112364 SCV000145128 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048605 SCV000587413 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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