Submissions for variant NM_007294.4(BRCA1):c.4399C>T (p.Gln1467Ter)

dbSNP: rs397509171

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000257306	SCV000323765	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	RCV000257306	SCV000325950	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496449	SCV001585362	pathogenic	Hereditary breast ovarian cancer syndrome	2023-08-16	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and uterine cancer (PMID: 19656415, 21702907). ClinVar contains an entry for this variant (Variation ID: 55191). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln1467*) 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).
Color Diagnostics, LLC DBA Color Health	RCV001525143	SCV001735185	pathogenic	Hereditary cancer-predisposing syndrome	2020-12-11	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 13 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics	RCV001525143	SCV005025853	pathogenic	Hereditary cancer-predisposing syndrome	2023-09-18	criteria provided, single submitter	clinical testing	The p.Q1467* pathogenic mutation (also known as c.4399C>T), located in coding exon 12 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4399. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This alteration was identified amongst 91 families in India with early onset breast and/or early onset ovarian cancer (Soumittra N et al. Hered Cancer Clin Pract, 2009 Aug;7:13). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496449	SCV000587395	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735468	SCV000863605	pathogenic	Breast and/or ovarian cancer	2010-07-07	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358297	SCV001553991	uncertain significance	not provided		no assertion criteria provided	clinical testing