Submissions for variant NM_007294.4(BRCA1):c.2983A>T (p.Lys995Ter)

dbSNP: rs879255315

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000661078	SCV000783325	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2017-12-15	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneKor MSA	RCV000238695	SCV000296769	pathogenic	not provided	2020-01-01	criteria provided, single submitter	clinical testing	This variant is a single amino acid change from Lysine to a Termination codon at amino acid residue 995 of the BRCA1 gene. It results in a truncated non-functional protein. Truncating variants in the BRCA1 gene are known to be pathogenic. The mutation database ClinVar contains entries for this variant (Variation ID: 252431).
GeneDx	RCV000238695	SCV000779470	pathogenic	not provided	2017-05-24	criteria provided, single submitter	clinical testing	This variant is denoted BRCA1 c.2983A>T at the cDNA level and p.Lys995Ter (K995X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAG>TAG), 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.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496586	SCV000587267	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research