ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1999C>T (p.Gln667Ter)

dbSNP: rs80356889
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Total submissions: 7
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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) RCV000111748 SCV000299682 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000162848 SCV000213335 pathogenic Hereditary cancer-predisposing syndrome 2018-09-10 criteria provided, single submitter clinical testing The p.Q667* pathogenic mutation (also known as c.1999C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 1999. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
GeneDx RCV000236983 SCV000293985 pathogenic not provided 2016-02-18 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.1999C>T at the cDNA level and p.Gln667Ter (Q667X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 2118C>T. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Color Diagnostics, LLC DBA Color Health RCV000162848 SCV000909356 pathogenic Hereditary cancer-predisposing syndrome 2021-09-15 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 10 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 detected in an individual with a personal or family history of breast or ovarian cancer (PMID: 32806537) and an individual affected with breast cancer (Color internal data). 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 (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000822 SCV001157887 pathogenic not specified 2018-09-17 criteria provided, single submitter clinical testing The BRCA1 c.1999C>T; p.Gln667Ter variant (rs80356889), to our knowledge, is not reported in the medical literature or in gene-specific databases. The variant is reported as pathogenic by several sources in the ClinVar database (Variation ID: 54430) and is absent general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Considering available information, this variant is classified as pathogenic.
Invitae RCV001388632 SCV001589704 pathogenic Hereditary breast ovarian cancer syndrome 2020-03-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 54430). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln667*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111748 SCV000144270 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2002-05-29 no assertion criteria provided clinical testing

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