ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3626del (p.Lys1208_Leu1209insTer)

dbSNP: rs80357571
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Total submissions: 10
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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) RCV000112140 SCV000299980 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 RCV000112140 SCV000325705 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000574479 SCV000665844 pathogenic Hereditary cancer-predisposing syndrome 2023-03-06 criteria provided, single submitter clinical testing The c.3626delT pathogenic mutation (also known as p.L1209*), located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at position 3626. This changes the amino acid from a leucine to a stop codon within coding exon 9. This pathogenic mutation has been observed in numerous breast and breast/ovarian cancer families, and is considered a founder mutation in Finland (Zelada-Hedman M et al. Cancer Res. 1997 Jun; 57(12):2474-7; Vehmanen P et al. Hum. Mol. Genet. 1997 Dec; 6(13):2309-15; Huusko P et al. Am. J. Hum. Genet. 1998 Jun; 62(6):1544-8; Sarantaus L et al. Eur. J. Hum. Genet. 2000 Oct; 8(10):757-63; Pelttari LM et al. Clin. Genet. 2018 Mar;93(3):595-602). Of note, this alteration is also designated as 3744delT and 3745delT in published literature. 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.
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269640 SCV001449765 pathogenic not provided 2014-06-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002298457 SCV002598866 pathogenic Hereditary breast ovarian cancer syndrome 2022-09-02 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3626delT (p.Leu1209X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251268 control chromosomes. c.3626delT has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (e.g. Li_2019, Xu_2021). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV002298457 SCV003441899 pathogenic Hereditary breast ovarian cancer syndrome 2023-11-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1209*) 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). This variant is present in population databases (rs80357571, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 9361038, 28802053). This variant is also known as 3744 delT. ClinVar contains an entry for this variant (Variation ID: 54943). For these reasons, this variant has been classified as Pathogenic.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV001269640 SCV004242821 pathogenic not provided 2024-02-06 criteria provided, single submitter clinical testing
OMIM RCV000112140 SCV000039549 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2000-10-01 no assertion criteria provided literature only
Breast Cancer Information Core (BIC) (BRCA1) RCV000112140 SCV000144816 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 1999-04-12 no assertion criteria provided clinical testing
BRCAlab, Lund University RCV000112140 SCV002589108 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2022-08-26 no assertion criteria provided clinical testing

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