NM_007294.3(BRCA1):c.4327C>T (p.Arg1443Ter) AND not provided

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

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Aug 18, 2017
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000235131.4

Allele description

NM_007294.3(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_007294.3(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_007299.3:c.1018C>T
NM_007300.3:c.4327C>T
NP_009225.1:p.Arg1443Ter
NP_009230.2:p.Arg340Ter
NP_009231.2:p.Arg1443Ter
LRG_292t1:c.4327C>T
LRG_292:g.135550C>T
LRG_292p1:p.Arg1443Ter
NC_000017.10:g.41234451G>A
NR_027676.1:n.4463C>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:

R1443*; ARG1443TER

Links:

OMIM: 113705.0016; dbSNP: rs41293455

NCBI 1000 Genomes Browser:

rs41293455

Molecular consequence:

NR_027676.1:n.4463C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_007294.3:c.4327C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000210173	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Aug 18, 2017)	germline	clinical testing	Citation Link,
SCV000296337	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest pathogenicity assessment criteria)	Pathogenic (May 8, 2015)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 23199084, 7894491, 22401979, 18680205, 15726418, 21324516, 9792861, 10682662, 26467025, 26295337
SCV000778740	Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	no assertion criteria provided	Pathogenic (Nov 28, 2016)	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000210173

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Aug 18, 2017)

germline

clinical testing

Citation Link,

SCV000296337

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest pathogenicity assessment criteria)

Pathogenic
(May 8, 2015)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

SCV000778740

Mayo Clinic Genetic Testing Laboratories,Mayo Clinic

no assertion criteria provided

Pathogenic
(Nov 28, 2016)

unknown

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control.

Janavičius R.

EPMA J. 2010 Sep;1(3):397-412. doi: 10.1007/s13167-010-0037-y. Epub 2010 Jun 27.

PubMed [citation]

PMID:: 23199084
PMCID:: PMC3405339

Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer.

Castilla LH, Couch FJ, Erdos MR, Hoskins KF, Calzone K, Garber JE, Boyd J, Lubin MB, Deshano ML, Brody LC, et al.

Nat Genet. 1994 Dec;8(4):387-91.

PubMed [citation]

PMID:: 7894491

See all PubMed Citations (10)

Details of each submission

From GeneDx, SCV000210173.11

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

Description

This pathogenic variant is denoted BRCA1 c.4327C>T at the cDNA level and p.Arg1443Ter (R1443X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also reported as BRCA1 4446C>T using alternate nomenclature, has been observed in multiple families with early-onset breast and ovarian cancer and has been reported as a recurrent variant in the French Canadian and Hispanic populations (Castilla 1994, Simard 2007, Zhang 2011, Weitzel 2013, Cruz-Correa 2017). We consider this variant to be pathogenic.

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000296337.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

#	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 Mayo Clinic Genetic Testing Laboratories,Mayo Clinic, SCV000778740.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 9, 2018

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