NM_007294.4(BRCA1):c.4327C>T (p.Arg1443Ter) AND Breast-ovarian cancer, familial 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (12 submissions)
Last evaluated:: Apr 22, 2016
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000019244.16

Allele description

NM_007294.4(BRCA1):c.4327C>T (p.Arg1443Ter)

Gene:

BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_007294.4(BRCA1):c.4327C>T (p.Arg1443Ter)

Other names:

p.R1443X:CGA>TGA

HGVS:

NC_000017.11:g.43082434G>A
NG_005905.2:g.135550C>T
NM_007294.3:c.4327C>T
NM_007294.4:c.4327C>TMANE SELECT
NM_007297.4:c.4186C>T
NM_007298.3:c.1018C>T
NM_007299.4:c.1018C>T
NM_007300.4:c.4327C>T
NP_009225.1:p.Arg1443Ter
NP_009225.1:p.Arg1443Ter
NP_009228.2:p.Arg1396Ter
NP_009229.2:p.Arg340Ter
NP_009230.2:p.Arg340Ter
NP_009231.2:p.Arg1443Ter
LRG_292t1:c.4327C>T
LRG_292:g.135550C>T
NC_000017.10:g.41234451G>A
NM_007299.3:c.1018C>T
NM_007300.3:c.4327C>T
NR_027676.2:n.4504C>T
U14680.1:n.4446C>T
p.Arg1443*
p.Arg1443X
p.Arg340*
p.R1443*
U14680.1:n.44446C>T

Nucleotide change:

4446C>T

Protein change:

R1396*; ARG1443TER

Links:

OMIM: 113705.0016; dbSNP: rs41293455

Molecular consequence:

NR_027676.2:n.4504C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_007294.3:c.4327C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_007294.4:c.4327C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_007297.4:c.4186C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_007298.3:c.1018C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_007299.4:c.1018C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_007300.4:c.4327C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

240

Condition(s)

Name:: Breast-ovarian cancer, familial 1 (BROVCA1)
Synonyms:: BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1; OVARIAN CANCER, SUSCEPTIBILITY TO; BREAST CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011450; MedGen: C2676676; Orphanet: 145; OMIM: 604370

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000039532	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 1994)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000109372	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Pathogenic (Nov 14, 2013)	germline	clinical testing
SCV000145057	Breast Cancer Information Core (BIC) (BRCA1)	no assertion criteria provided	Pathogenic (May 29, 2002)	germline	clinical testing
SCV000220762	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Pathogenic (Oct 2, 2014)	unknown	literature only	PubMed (14) [See all records that cite these PMIDs] 15726418, 18680205, 15883839, 16030099, 22401979, 22798144, 23341105, 21324516, 20694749, 19241424, 11179017, 7894491, 19863560, 17221156 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV000267710	Michigan Medical Genetics Laboratories,University of Michigan	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 21, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000282327	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015))	Pathogenic (Apr 22, 2016)	germline	curation	ENIGMA BRCA1/2 Classification Criteria (2015), Citation Link,
SCV000325921	Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	criteria provided, single submitter (CIMBA Mutation Classification guidelines May 2016)	Pathogenic (Oct 2, 2015)	germline	clinical testing	CIMBA_Mutation_Classification_guidelines_May16.pdf, Citation Link,
SCV000577931	Genologica Medica See additional submitters Servicio Andaluz de Salud,Hospital Universitario Virgen de la Victoria	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 1, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000593678	Genetic Services Laboratory,University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 29, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000733611	Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV000743394	Genome Diagnostics Laboratory,University Medical Center Utrecht - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Oct 8, 2014)	germline	clinical testing	Citation Link,
SCV000744615	DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Sep 21, 2015)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	41	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	29	not provided	not provided	29	not provided	literature only, clinical testing
not provided	germline	unknown	not provided	239	not provided	not provided	not provided	clinical testing, curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	literature only
African	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Ashkenazi	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Caucasian	germline	yes	8	not provided	not provided	not provided	not provided	clinical testing
Caucasian Non Hispanic	germline	yes	5	not provided	not provided	not provided	not provided	clinical testing
Causasians	germline	yes	not provided	1	not provided	not provided	yes	clinical testing
Central/Eastern European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
French Canadian	germline	yes	19	not provided	not provided	not provided	not provided	clinical testing
French Canadian, English	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
French Canadian, Welsh	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Latin American, Caribbean	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
Latin American, Caribbean, Mexican	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Native American	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European	germline	yes	35	not provided	not provided	not provided	not provided	clinical testing
Western European, African	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European, Central/Eastern European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European, French Canadian	germline	yes	10	not provided	not provided	not provided	not provided	clinical testing
Western European, French, Candian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European, Native American	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western EuropeanAsianLatin American	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

BRCA1 variants in a family study of African-American and Latina women.

McKean-Cowdin R, Spencer Feigelson H, Xia LY, Pearce CL, Thomas DC, Stram DO, Henderson BE.

Hum Genet. 2005 May;116(6):497-506. Epub 2005 Feb 23.

PubMed [citation]

PMID:: 15726418

A yeast recombination assay to characterize human BRCA1 missense variants of unknown pathological significance.

Caligo MA, Bonatti F, Guidugli L, Aretini P, Galli A.

Hum Mutat. 2009 Jan;30(1):123-33. doi: 10.1002/humu.20817.

PubMed [citation]

PMID:: 18680205

See all PubMed Citations (15)

Details of each submission

From OMIM, SCV000039532.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

Castilla et al. (1994) studied 50 probands with a family history of breast and/or ovarian cancer (604370) for germline mutations in the coding region of the BRCA1 candidate gene. They identified a C-to-T substitution at position 4446 of the BRCA1 gene, leading to a premature termination codon in place of arginine-1443 and a truncated protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Sharing Clinical Reports Project (SCRP), SCV000109372.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	29	not provided	not provided		not provided	not provided	not provided	not provided

From Breast Cancer Information Core (BIC) (BRCA1), SCV000145057.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	32	not provided	not provided	clinical testing	not provided
2	not provided	3	not provided	not provided	clinical testing	not provided
3	not provided	1	not provided	not provided	clinical testing	not provided
4	not provided	2	not provided	not provided	clinical testing	not provided
5	not provided	3	not provided	not provided	clinical testing	not provided
6	African	1	not provided	not provided	clinical testing	not provided
7	Ashkenazi	1	not provided	not provided	clinical testing	not provided
8	Caucasian	2	not provided	not provided	clinical testing	not provided
9	Caucasian	1	not provided	not provided	clinical testing	not provided
10	Caucasian	2	not provided	not provided	clinical testing	not provided
11	Caucasian	3	not provided	not provided	clinical testing	not provided
12	Caucasian Non Hispanic	5	not provided	not provided	clinical testing	not provided
13	Central/Eastern European	1	not provided	not provided	clinical testing	not provided
14	French Canadian	19	not provided	not provided	clinical testing	not provided
15	French Canadian, English	1	not provided	not provided	clinical testing	not provided
16	French Canadian, Welsh	1	not provided	not provided	clinical testing	not provided
17	Latin American, Caribbean	3	not provided	not provided	clinical testing	not provided
18	Latin American, Caribbean, Mexican	1	not provided	not provided	clinical testing	not provided
19	Native American	1	not provided	not provided	clinical testing	not provided
20	Western European	35	not provided	not provided	clinical testing	not provided
21	Western European, African	1	not provided	not provided	clinical testing	not provided
22	Western European, Central/Eastern European	1	not provided	not provided	clinical testing	not provided
23	Western European, French Canadian	10	not provided	not provided	clinical testing	not provided
24	Western European, French, Candian	1	not provided	not provided	clinical testing	not provided
25	Western European, Native American	1	not provided	not provided	clinical testing	not provided
26	Western EuropeanAsianLatin American	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		32	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided
3	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
4	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided
5	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided
6	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
7	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
8	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided
9	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
10	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided
11	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided
12	germline	yes	not provided	not provided	not provided		5	not provided	not provided	not provided
13	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
14	germline	yes	not provided	not provided	not provided		19	not provided	not provided	not provided
15	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
16	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
17	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided
18	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
19	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
20	germline	yes	not provided	not provided	not provided		35	not provided	not provided	not provided
21	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
22	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
23	germline	yes	not provided	not provided	not provided		10	not provided	not provided	not provided
24	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
25	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
26	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Counsyl, SCV000220762.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (14)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Michigan Medical Genetics Laboratories,University of Michigan, SCV000267710.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	Blood	not provided		not provided	not provided	not provided	not provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000282327.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

Variant allele predicted to encode a truncated non-functional protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000325921.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	239	not provided

From Genologica Medica, SCV000577931.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Causasians	not provided	not provided	yes	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	Blood	not provided		not provided	not provided	1	not provided

From Genetic Services Laboratory,University of Chicago, SCV000593678.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen - VKGL Data-share Consensus, SCV000733611.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory,University Medical Center Utrecht - VKGL Data-share Consensus, SCV000743394.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensus, SCV000744615.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 27, 2020

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