NM_000548.5(TSC2):c.5393C>T (p.Ser1798Phe) AND Tuberous sclerosis 2

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 10, 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:: RCV001039901.7

Allele description

NM_000548.5(TSC2):c.5393C>T (p.Ser1798Phe)

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.5393C>T (p.Ser1798Phe)

HGVS:

NC_000016.10:g.2088579C>T
NG_005895.1:g.44274C>T
NG_008617.1:g.54642G>A
NM_000548.5:c.5393C>TMANE SELECT
NM_001077183.3:c.5192C>T
NM_001114382.3:c.5324C>T
NM_001318827.2:c.5084C>T
NM_001318829.2:c.5048C>T
NM_001318831.2:c.4661C>T
NM_001318832.2:c.5225C>T
NM_001363528.2:c.5195C>T
NM_001370404.1:c.5261C>T
NM_001370405.1:c.5252C>T
NM_021055.3:c.5264C>T
NP_000539.2:p.Ser1798Phe
NP_001070651.1:p.Ser1731Phe
NP_001107854.1:p.Ser1775Phe
NP_001305756.1:p.Ser1695Phe
NP_001305758.1:p.Ser1683Phe
NP_001305760.1:p.Ser1554Phe
NP_001305761.1:p.Ser1742Phe
NP_001350457.1:p.Ser1732Phe
NP_001357333.1:p.Ser1754Phe
NP_001357334.1:p.Ser1751Phe
NP_066399.2:p.Ser1755Phe
LRG_487t1:c.5393C>T
LRG_487:g.44274C>T
NC_000016.9:g.2138580C>T
NM_000548.3:c.5393C>T

Protein change:

S1554F

Links:

dbSNP: rs2091216208

NCBI 1000 Genomes Browser:

rs2091216208

Molecular consequence:

NM_000548.5:c.5393C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.5192C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.5324C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.5084C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.5048C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.4661C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.5225C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.5195C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.5261C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.5252C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.5264C>T - 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
SCV001203451	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 10, 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

SCV001203451

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 10, 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 Invitae, SCV001203451.5

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

Description

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: 838366). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1798 of the TSC2 protein (p.Ser1798Phe).

#	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: May 1, 2024

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