NM_000548.5(TSC2):c.3986G>A (p.Arg1329His) AND not specified

Germline classification:: Benign (8 submissions)
Last evaluated:: Sep 1, 2020
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:: RCV000118707.33

Allele description [Variation Report for NM_000548.5(TSC2):c.3986G>A (p.Arg1329His)]

NM_000548.5(TSC2):c.3986G>A (p.Arg1329His)

Gene:

TSC2:TSC complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000548.5(TSC2):c.3986G>A (p.Arg1329His)

Other names:

NM_000548.3(TSC2):c.3986G>A(p.Arg1329His); NM_001077183.1(TSC2):c.3785G>A(p.Arg1262His); NM_001114382.1(TSC2):c.3917G>A(p.Arg1306His)

HGVS:

NC_000016.10:g.2083797G>A
NG_005895.1:g.39492G>A
NM_000548.5:c.3986G>AMANE SELECT
NM_001077183.3:c.3785G>A
NM_001114382.3:c.3917G>A
NM_001318827.2:c.3677G>A
NM_001318829.2:c.3641G>A
NM_001318831.2:c.3254G>A
NM_001318832.2:c.3818G>A
NM_001363528.2:c.3788G>A
NM_001370404.1:c.3854G>A
NM_001370405.1:c.3857G>A
NM_021055.3:c.3857G>A
NP_000539.2:p.Arg1329His
NP_001070651.1:p.Arg1262His
NP_001107854.1:p.Arg1306His
NP_001305756.1:p.Arg1226His
NP_001305758.1:p.Arg1214His
NP_001305760.1:p.Arg1085His
NP_001305761.1:p.Arg1273His
NP_001350457.1:p.Arg1263His
NP_001357333.1:p.Arg1285His
NP_001357334.1:p.Arg1286His
NP_066399.2:p.Arg1286His
LRG_487t1:c.3986G>A
LRG_487:g.39492G>A
NC_000016.9:g.2133798G>A
NM_000548.3:c.3986G>A
NM_000548.4:c.3986G>A
P49815:p.Arg1329His
p.R1329H
p.(Arg1329His)

Protein change:

R1085H

Links:

Tuberous sclerosis database (TSC2): TSC2_00092; UniProtKB: P49815#VAR_008029; dbSNP: rs45517323

NCBI 1000 Genomes Browser:

rs45517323

Molecular consequence:

NM_000548.5:c.3986G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.3785G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.3917G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.3677G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.3641G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.3254G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.3818G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.3788G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.3854G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.3857G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.3857G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000086453	ITMI	no classification provided	not provided	germline	reference population	PubMed (1) [See all records that cite this PMID]
SCV000153122	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Sep 1, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000229649	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (Apr 21, 2015)	germline	clinical testing	Citation Link,
SCV000305212	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001808073	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Benign	germline	clinical testing
SCV001921901	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV001973273	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV002035361	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
African	germline	unknown	not provided	not provided	not provided	43	not provided	reference population
African_European	germline	unknown	not provided	not provided	not provided	46	not provided	reference population
Central_Asian	germline	unknown	not provided	not provided	not provided	50	not provided	reference population
East_Asian	germline	unknown	not provided	not provided	not provided	62	not provided	reference population
European	germline	unknown	not provided	not provided	not provided	331	not provided	reference population
Hispanic	germline	unknown	not provided	not provided	not provided	118	not provided	reference population
Whole_cohort	germline	unknown	not provided	not provided	not provided	681	not provided	reference population

Citations

PubMed

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]

PMID:: 24728327
PMCID:: PMC3984285

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From ITMI, SCV000086453.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	African	not provided	not provided	not provided	reference population	PubMed (1)
2	African_European	not provided	not provided	not provided	reference population	PubMed (1)
3	Central_Asian	not provided	not provided	not provided	reference population	PubMed (1)
4	East_Asian	not provided	not provided	not provided	reference population	PubMed (1)
5	European	not provided	not provided	not provided	reference population	PubMed (1)
6	Hispanic	not provided	not provided	not provided	reference population	PubMed (1)
7	Whole_cohort	not provided	not provided	not provided	reference population	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	43	not provided	discovery		not provided	0.0698	not provided	not provided
2	germline	unknown	46	not provided	discovery		not provided	0.0341	not provided	not provided
3	germline	unknown	50	not provided	discovery		not provided	0	not provided	not provided
4	germline	unknown	62	not provided	discovery		not provided	0	not provided	not provided
5	germline	unknown	331	not provided	discovery		not provided	0	not provided	not provided
6	germline	unknown	118	not provided	discovery		not provided	0.0042	not provided	not provided
7	germline	unknown	681	not provided	discovery		not provided	0.0074	not provided	not provided

From Genetic Services Laboratory, University of Chicago, SCV000153122.3

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000229649.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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		3	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000305212.1

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

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001808073.1

#	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 Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001921901.1

#	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 Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001973273.1

#	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 Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV002035361.1

#	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: Nov 24, 2024

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