ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4372C>T (p.Gln1458Ter) (rs80356932)

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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) RCV000112328 SCV000300109 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000131884 SCV000186939 pathogenic Hereditary cancer-predisposing syndrome 2014-12-23 criteria provided, single submitter clinical testing The p.Q1458* pathogenic mutation (also known as c.4372C>T and 4491C>T), located in coding exon 12 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4372. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This mutation was reported in the Hong Kong Hereditary Breast Cancer Family Registry (Kwong A et al. Breast Cancer Res. Treat. 2009; 117:683-6). The p.Q1458* mutation has also been reported in a French family with a strong history of breast cancers (Rostagno P et al. J Hum Genet. 2003;48(7):362-6). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112328 SCV000325941 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131884 SCV000683177 pathogenic Hereditary cancer-predisposing syndrome 2020-12-21 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 13 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 19353265, 21120943, 24578176, 25480878). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease ( Based on the available evidence, this variant is classified as Pathogenic.
GeneDx RCV000657617 SCV000779359 pathogenic not provided 2018-09-18 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4372C>T at the cDNA level and p.Gln1458Ter (Q1458X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with breast and/or ovarian cancer (Tang 1999, Caux-Moncoutier 2011, Kang 2014, Wang 2015) and is considered pathogenic.
Invitae RCV001381001 SCV001579249 pathogenic Hereditary breast and ovarian cancer syndrome 2019-11-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1458*) 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 with breast cancer and ovarian cancer (PMID: 30702160, 28724667, 29446198, 29752822, 30078507). ClinVar contains an entry for this variant (Variation ID: 55183). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112328 SCV000145077 not provided Breast-ovarian cancer, familial 1 no assertion provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000657617 SCV000591513 uncertain significance not provided no assertion criteria provided clinical testing

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