ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3991C>T (p.Gln1331Ter)

dbSNP: rs397507224
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Total submissions: 5
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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) RCV000031139 SCV000300052 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031139 SCV000325808 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV001852618 SCV002153067 pathogenic Hereditary breast ovarian cancer syndrome 2022-02-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1331*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 37558). This premature translational stop signal has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 22798144, 29446198). This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV002354176 SCV002622481 pathogenic Hereditary cancer-predisposing syndrome 2020-11-05 criteria provided, single submitter clinical testing The p.Q1331* pathogenic mutation (also known as c.3991C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 3991. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration was identified in multiple individuals with breast and/or ovarian cancer (Kim H et al. Breast Cancer Res Treat, 2012 Aug;134:1315-26; Choi MC et al. Int J Gynecol Cancer, 2018 02;28:308-315; Kwon BS et al. Cancer Res Treat, 2019 Jul;51:941-950; Ryu JM et al. Breast Cancer Res Treat, 2019 Jan;173:385-3950; Shin HC et al. Cancer Res Treat, 2020 Jul;52:697-713). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). In addition to the clinical data presented in the literature, 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.
Sharing Clinical Reports Project (SCRP) RCV000031139 SCV000053738 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2011-09-20 no assertion criteria provided clinical testing

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