Submissions for variant NM_007294.4(BRCA1):c.4503C>A (p.Cys1501Ter)

dbSNP: rs747539984

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000256519	SCV000323772	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-10-18	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	RCV000256519	SCV000325989	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV000472996	SCV000549326	pathogenic	Hereditary breast ovarian cancer syndrome	2021-11-12	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 266478). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 25948282). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys1501*) 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).
Department of Molecular Diagnostics, Institute of Oncology Ljubljana	RCV000256519	SCV001499711	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2020-04-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000472996	SCV004039085	pathogenic	Hereditary breast ovarian cancer syndrome	2023-08-11	criteria provided, single submitter	clinical testing	Variant summary: BRCA1 c.4503C>A (p.Cys1501X) 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. The variant was absent in 251274 control chromosomes. c.4503C>A has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (eg. Klusa_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	RCV001640594	SCV001852770	pathogenic	Ovarian carcinoma	2021-09-12	no assertion criteria provided	clinical testing