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NM_007294.4(BRCA1):c.2006T>C (p.Met669Thr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(1);Likely benign(4);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
10 (Most recent: Sep 9, 2021)
Last evaluated:
Oct 28, 2020
Accession:
VCV000037442.8
Variation ID:
37442
Description:
single nucleotide variant
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NM_007294.4(BRCA1):c.2006T>C (p.Met669Thr)

Allele ID
45998
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43093525 (GRCh38) GRCh38 UCSC
17: 41245542 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_292:g.124459T>C
LRG_292t1:c.2006T>C LRG_292p1:p.Met669Thr
NC_000017.11:g.43093525A>G
... more HGVS
Protein change
M669T, M622T
Other names
2125T>C
Canonical SPDI
NC_000017.11:43093524:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (G)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00006
1000 Genomes Project 0.00020
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00005
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Links
ClinGen: CA001337
dbSNP: rs80356895
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 1 criteria provided, single submitter Jan 3, 2018 RCV000420884.3
Likely benign 1 criteria provided, single submitter Oct 28, 2020 RCV001472789.1
Likely benign 1 criteria provided, single submitter Jan 20, 2020 RCV001659763.1
Conflicting interpretations of pathogenicity 5 criteria provided, conflicting interpretations May 28, 2019 RCV000031023.8
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Aug 17, 2020 RCV000130064.6
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRCA1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
12270 12437

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Benign
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: unknown
Mendelics
Accession: SCV001140587.1
Submitted: (Oct 22, 2019)
Evidence details
Uncertain significance
(Dec 01, 2015)
criteria provided, single submitter
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: unknown
Counsyl
Accession: SCV000487917.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (1)
Likely benign
(Jan 03, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000518172.4
Submitted: (Mar 26, 2018)
Evidence details
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
Likely benign
(Sep 23, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000911034.1
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(Aug 17, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000184891.6
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
The p.M669T variant (also known as c.2006T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide … (more)
Likely benign
(Oct 28, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV001676927.1
Submitted: (Jan 07, 2021)
Evidence details
Likely benign
(Jan 20, 2020)
criteria provided, single submitter
Method: curation
Breast-ovarian cancer, familial 1
Breast-ovarian cancer, familial 2
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Research and Development, ARUP Laboratories
Accession: SCV001878216.1
Submitted: (Sep 09, 2021)
Evidence details
Publications
PubMed (1)
Other databases
https://arup.utah.edu/database/B…
Benign
(Feb 17, 2012)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053616.3
Submitted: (Jun 20, 2012)
Evidence details
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591363.2
Submitted: (Mar 31, 2021)
Evidence details
Comment:
The BRCA1 p.Met669Thr variant was identified in 4 of 926 proband chromosomes (frequency: 0.004) from individuals or families with breast cancer and was not identified … (more)
Uncertain significance
(Nov 25, 2004)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144273.1
Submitted: (Mar 28, 2014)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. Parsons MT Human mutation 2019 PMID: 31131967
Prevalence of BRCA1 gene mutation in breast cancer patients in Guangxi, China. Sun L International journal of clinical and experimental pathology 2014 PMID: 25337278
https://arup.utah.edu/database/BRCA/Variants/BRCA1.php - - - -

Text-mined citations for rs80356895...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 18, 2021