Submissions for variant NM_007294.4(BRCA1):c.4258C>T (p.Gln1420Ter) (rs80357305)

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077569	SCV000300098	pathogenic	Breast-ovarian cancer, familial 1	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneDx	RCV000236776	SCV000292522	pathogenic	not provided	2015-11-19	criteria provided, single submitter	clinical testing	This pathogenic variant is denoted BRCA1 c.4258C>T at the cDNA level and p.Gln1420Ter (Q1420X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also published as c.4377C>T using alternate nomenclature, has been reported in multiple patients with breast or ovarian cancer (Thirthagiri 2008, Minucci 2015, Couch 2015). Based on currently available evidence, we consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000077569	SCV000296323	pathogenic	Breast-ovarian cancer, familial 1	2015-04-08	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000077569	SCV000325908	pathogenic	Breast-ovarian cancer, familial 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000077569	SCV000693534	pathogenic	Breast-ovarian cancer, familial 1	2020-01-01	criteria provided, single submitter	clinical testing	This variant is a single amino acid change from Glutamine to a Termination codon at amino acid residue 1420 of the BRCA1 gene. It is expected to result in a truncated, non-functional protein. This variant is also known as c.4377C>T in the literature has been reported in patients with breast and/or ovarian cancer (PMID: 18627636, 26306726). The mutation database ClinVar contains entries for this variant (Variation ID: 55155).
Mendelics	RCV000496798	SCV000839238	pathogenic	Hereditary breast and ovarian cancer syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001022156	SCV001183856	pathogenic	Hereditary cancer-predisposing syndrome	2018-04-03	criteria provided, single submitter	clinical testing	Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Institute of Genomics,University of Tartu	RCV000077569	SCV001430698	pathogenic	Breast-ovarian cancer, familial 1		criteria provided, single submitter	research
Sharing Clinical Reports Project (SCRP)	RCV000077569	SCV000109371	pathogenic	Breast-ovarian cancer, familial 1	2013-04-24	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077569	SCV000145043	pathogenic	Breast-ovarian cancer, familial 1	1999-06-22	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto	RCV000496798	SCV000587385	pathogenic	Hereditary breast and ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research