NM_000548.5(TSC2):c.119T>C (p.Ile40Thr) AND Tuberous sclerosis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 9, 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:: RCV003626606.2

Allele description [Variation Report for NM_000548.5(TSC2):c.119T>C (p.Ile40Thr)]

NM_000548.5(TSC2):c.119T>C (p.Ile40Thr)

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.119T>C (p.Ile40Thr)

HGVS:

NC_000016.10:g.2048734T>C
NG_005895.1:g.4429T>C
NG_008412.1:g.4133A>G
NM_000548.5:c.119T>CMANE SELECT
NM_001077183.3:c.119T>C
NM_001114382.3:c.119T>C
NM_001318827.2:c.119T>C
NM_001318829.2:c.-10+669T>C
NM_001318831.2:c.-108T>C
NM_001318832.2:c.152T>C
NM_001363528.2:c.119T>C
NM_001370404.1:c.119T>C
NM_001370405.1:c.119T>C
NM_021055.3:c.119T>C
NP_000539.2:p.Ile40Thr
NP_001070651.1:p.Ile40Thr
NP_001107854.1:p.Ile40Thr
NP_001305756.1:p.Ile40Thr
NP_001305761.1:p.Ile51Thr
NP_001350457.1:p.Ile40Thr
NP_001357333.1:p.Ile40Thr
NP_001357334.1:p.Ile40Thr
NP_066399.2:p.Ile40Thr
LRG_487t1:c.119T>C
LRG_1366:g.4133A>G
LRG_487:g.4429T>C
NC_000016.9:g.2098735T>C
NM_000548.3:c.119T>C
p.I40T

Protein change:

I40T

Links:

dbSNP: rs587781758

NCBI 1000 Genomes Browser:

rs587781758

Molecular consequence:

NM_001318831.2:c.-108T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001318829.2:c.-10+669T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000548.5:c.119T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.119T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.119T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.119T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.152T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.119T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.119T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.119T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.119T>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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Flavobacterium sp. IH3-5 16S ribosomal RNA gene, partial sequence
Flavobacterium sp. IH3-5 16S ribosomal RNA gene, partial sequence
gi|55831331|gb|AY789577.1|

Nucleotide
uncharacterized protein Dmel_CG5056 [Drosophila melanogaster]
uncharacterized protein Dmel_CG5056 [Drosophila melanogaster]
gi|24583382|ref|NP_609391.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004504496	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 9, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004504496

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 9, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004504496.1

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

Description

This variant is not present in population databases (gnomAD no frequency). 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. 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. ClinVar contains an entry for this variant (Variation ID: 141455). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 40 of the TSC2 protein (p.Ile40Thr).

#	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: Sep 29, 2024

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