NM_000548.5(TSC2):c.5383C>T (p.Arg1795Cys) AND not specified

Germline classification:: Likely benign (4 submissions)
Last evaluated:: Dec 27, 2021
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:: RCV000178483.25

Allele description [Variation Report for NM_000548.5(TSC2):c.5383C>T (p.Arg1795Cys)]

NM_000548.5(TSC2):c.5383C>T (p.Arg1795Cys)

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.5383C>T (p.Arg1795Cys)

Other names:

p.R1795C:CGC>TGC

HGVS:

NC_000016.10:g.2088569C>T
NG_005895.1:g.44264C>T
NG_008617.1:g.54652G>A
NM_000548.5:c.5383C>TMANE SELECT
NM_001077183.3:c.5182C>T
NM_001114382.3:c.5314C>T
NM_001318827.2:c.5074C>T
NM_001318829.2:c.5038C>T
NM_001318831.2:c.4651C>T
NM_001318832.2:c.5215C>T
NM_001363528.2:c.5185C>T
NM_001370404.1:c.5251C>T
NM_001370405.1:c.5242C>T
NM_021055.3:c.5254C>T
NP_000539.2:p.Arg1795Cys
NP_001070651.1:p.Arg1728Cys
NP_001107854.1:p.Arg1772Cys
NP_001305756.1:p.Arg1692Cys
NP_001305758.1:p.Arg1680Cys
NP_001305760.1:p.Arg1551Cys
NP_001305761.1:p.Arg1739Cys
NP_001350457.1:p.Arg1729Cys
NP_001357333.1:p.Arg1751Cys
NP_001357334.1:p.Arg1748Cys
NP_066399.2:p.Arg1752Cys
LRG_487t1:c.5383C>T
LRG_487:g.44264C>T
NC_000016.9:g.2138570C>T
NM_000548.3:c.5383C>T
p.R1795C
p.(Arg1795Cys)

Protein change:

R1551C

Links:

Tuberous sclerosis database (TSC2): TSC2_00666; dbSNP: rs45517423

NCBI 1000 Genomes Browser:

rs45517423

Molecular consequence:

NM_000548.5:c.5383C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.5182C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.5314C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.5074C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.5038C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.4651C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.5215C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.5185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.5251C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.5242C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.5254C>T - 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
SCV000230568	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely benign (Jul 15, 2014)	germline	clinical testing	Citation Link,
SCV000249208	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Dec 27, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000540604	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Jan 24, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001965340	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

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Eurofins Ntd Llc (ga), SCV000230568.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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		2	not provided	not provided	not provided

From Genetic Services Laboratory, University of Chicago, SCV000249208.2

#	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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000540604.1

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

Description

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is classified in HGMD as DM and seen in 7 papers, including in patients who inherited the mutation from unaffected parents. This variant is present in gnomAD with a Max MAF of 0.36% of Ashkenazi Jews (36/10110 chrs and homozygous in 1 Latino). High for tuberous sclerosis incidence of 1/25000-1/11300. The variant is classified with 1 star in ClinVar as VUS by 3 submitters (CSER_CC_NCGL, University of Chicago, and Ambry), Likely benign by 3 submitters (Emory, Invitae, Biesecker), and Benign by GeneDx.

#	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 Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001965340.1

#	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 29, 2024

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