NM_000548.5(TSC2):c.3097T>C (p.Tyr1033His) AND Tuberous sclerosis 2

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 6, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001043250.5

Allele description

NM_000548.5(TSC2):c.3097T>C (p.Tyr1033His)

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.3097T>C (p.Tyr1033His)

HGVS:

NC_000016.10:g.2079162T>C
NG_005895.1:g.34857T>C
NM_000548.5:c.3097T>CMANE SELECT
NM_001077183.3:c.2965T>C
NM_001114382.3:c.3097T>C
NM_001318827.2:c.2857T>C
NM_001318829.2:c.2821T>C
NM_001318831.2:c.2365T>C
NM_001318832.2:c.2998T>C
NM_001363528.2:c.2968T>C
NM_001370404.1:c.2965T>C
NM_001370405.1:c.2968T>C
NM_021055.3:c.2968T>C
NP_000539.2:p.Tyr1033His
NP_001070651.1:p.Tyr989His
NP_001107854.1:p.Tyr1033His
NP_001305756.1:p.Tyr953His
NP_001305758.1:p.Tyr941His
NP_001305760.1:p.Tyr789His
NP_001305761.1:p.Tyr1000His
NP_001350457.1:p.Tyr990His
NP_001357333.1:p.Tyr989His
NP_001357334.1:p.Tyr990His
NP_066399.2:p.Tyr990His
LRG_487t1:c.3097T>C
LRG_487:g.34857T>C
NC_000016.9:g.2129163T>C
NM_000548.3:c.3097T>C
p.(Tyr1033His)

Protein change:

Y1000H

Links:

Tuberous sclerosis database (TSC2): TSC2_01132; dbSNP: rs137854404

NCBI 1000 Genomes Browser:

rs137854404

Molecular consequence:

NM_000548.5:c.3097T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.2965T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.3097T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.2857T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.2821T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.2365T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.2998T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.2968T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.2965T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.2968T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.2968T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Tuberous sclerosis 2 (TSC2)
Identifiers:: MONDO: MONDO:0013199; MedGen: C1860707; Orphanet: 805; OMIM: 613254

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001206974	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22903760, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001206974

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 6, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Functional assessment of TSC2 variants identified in individuals with tuberous sclerosis complex.

Hoogeveen-Westerveld M, Ekong R, Povey S, Mayer K, Lannoy N, Elmslie F, Bebin M, Dies K, Thompson C, Sparagana SP, Davies P, van Eeghen AM, Thiele EA, van den Ouweland A, Halley D, Nellist M.

Hum Mutat. 2013 Jan;34(1):167-75. doi: 10.1002/humu.22202. Epub 2012 Oct 11. Erratum in: Hum Mutat. 2013 Feb;34(2):408-10. van Eeghen, Agnies M [added]; Thiele, Elizabeth A [added].

PubMed [citation]

PMID:: 22903760

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001206974.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

ClinVar contains an entry for this variant (Variation ID: 50040). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change does not substantially affect TSC2 function (PMID: 22903760). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function. This missense change has been observed in individual(s) with tuberous sclerosis complex (PMID: 22903760). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1033 of the TSC2 protein (p.Tyr1033His).

#	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

Last Updated: Jun 2, 2024

ClinVar

Relating variation to medicine