NM_000548.5(TSC2):c.1447G>C (p.Glu483Gln) AND Tuberous sclerosis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 26, 2022
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:: RCV001924040.6

Allele description [Variation Report for NM_000548.5(TSC2):c.1447G>C (p.Glu483Gln)]

NM_000548.5(TSC2):c.1447G>C (p.Glu483Gln)

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.1447G>C (p.Glu483Gln)

HGVS:

NC_000016.10:g.2064275G>C
NG_005895.1:g.19970G>C
NM_000548.5:c.1447G>CMANE SELECT
NM_001077183.3:c.1447G>C
NM_001114382.3:c.1447G>C
NM_001318827.2:c.1336G>C
NM_001318829.2:c.1300G>C
NM_001318831.2:c.847G>C
NM_001318832.2:c.1480G>C
NM_001363528.2:c.1447G>C
NM_001370404.1:c.1447G>C
NM_001370405.1:c.1447G>C
NM_021055.3:c.1447G>C
NP_000539.2:p.Glu483Gln
NP_001070651.1:p.Glu483Gln
NP_001107854.1:p.Glu483Gln
NP_001305756.1:p.Glu446Gln
NP_001305758.1:p.Glu434Gln
NP_001305760.1:p.Glu283Gln
NP_001305761.1:p.Glu494Gln
NP_001350457.1:p.Glu483Gln
NP_001357333.1:p.Glu483Gln
NP_001357334.1:p.Glu483Gln
NP_066399.2:p.Glu483Gln
LRG_487:g.19970G>C
NC_000016.9:g.2114276G>C

Protein change:

E283Q

Links:

dbSNP: rs397515297

NCBI 1000 Genomes Browser:

rs397515297

Molecular consequence:

NM_000548.5:c.1447G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.1447G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.1447G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.1336G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.1300G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.847G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.1480G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.1447G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.1447G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.1447G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.1447G>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
SCV002200314	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 26, 2022)	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

SCV002200314

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 26, 2022)

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, SCV002200314.3

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

Description

ClinVar contains an entry for this variant (Variation ID: 1424794). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 483 of the TSC2 protein (p.Glu483Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. 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. 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.

#	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

ClinVar

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