ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4523G>A (p.Trp1508Ter) (rs786202631)

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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) RCV000241110 SCV000300133 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 RCV000165536 SCV000216268 pathogenic Hereditary cancer-predisposing syndrome 2016-10-17 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 RCV000508652 SCV000605881 pathogenic not provided 2016-12-19 criteria provided, single submitter clinical testing
GeneDx RCV000508652 SCV000617445 pathogenic not provided 2017-08-02 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4523G>A at the cDNA level and p.Trp1508Ter (W1508X) at theprotein level. Using alternate nomenclature, this variant would be defined as 4642G>A. The substitution creates anonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TAG), and is predicted to cause lossof normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has beenreported in at least three women with breast cancer (Lynce 2015, Rummel 2013, Wong-Brown 2015) and is consideredpathogenic.
Color RCV000165536 SCV000905201 pathogenic Hereditary cancer-predisposing syndrome 2017-11-13 criteria provided, single submitter clinical testing
Invitae RCV000793994 SCV000933376 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1508*) 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 an individual affected with breast cancer (PMID: 25682074). ClinVar contains an entry for this variant (Variation ID: 186016). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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