NM_000548.5(TSC2):c.3796C>G (p.Leu1266Val) AND Tuberous sclerosis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 21, 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:: RCV003626714.2

Allele description [Variation Report for NM_000548.5(TSC2):c.3796C>G (p.Leu1266Val)]

NM_000548.5(TSC2):c.3796C>G (p.Leu1266Val)

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.3796C>G (p.Leu1266Val)

HGVS:

NC_000016.10:g.2081780C>G
NG_005895.1:g.37475C>G
NM_000548.5:c.3796C>GMANE SELECT
NM_001077183.3:c.3664C>G
NM_001114382.3:c.3796C>G
NM_001318827.2:c.3556C>G
NM_001318829.2:c.3520C>G
NM_001318831.2:c.3064C>G
NM_001318832.2:c.3697C>G
NM_001363528.2:c.3667C>G
NM_001370404.1:c.3664C>G
NM_001370405.1:c.3667C>G
NM_001406663.1:c.3793C>G
NM_001406664.1:c.3793C>G
NM_001406665.1:c.3664C>G
NM_001406667.1:c.3757C>G
NM_001406668.1:c.3754C>G
NM_001406670.1:c.3685C>G
NM_001406671.1:c.3655C>G
NM_001406673.1:c.3652C>G
NM_001406675.1:c.3649C>G
NM_001406676.1:c.3646C>G
NM_001406677.1:c.3607C>G
NM_001406678.1:c.3553C>G
NM_001406679.1:c.3517C>G
NM_001406680.1:c.3196C>G
NM_001406681.1:c.3205C>G
NM_001406682.1:c.3196C>G
NM_001406683.1:c.3196C>G
NM_001406684.1:c.3193C>G
NM_001406685.1:c.3067C>G
NM_001406686.1:c.3067C>G
NM_001406687.1:c.3064C>G
NM_001406688.1:c.3064C>G
NM_001406689.1:c.2452C>G
NM_001406690.1:c.2323C>G
NM_001406691.1:c.2320C>G
NM_001406692.1:c.2323C>G
NM_001406693.1:c.2323C>G
NM_001406694.1:c.2323C>G
NM_001406695.1:c.2320C>G
NM_001406696.1:c.2320C>G
NM_001406697.1:c.2320C>G
NM_001406698.1:c.2062C>G
NM_021055.3:c.3667C>G
NP_000539.2:p.Leu1266Val
NP_000539.2:p.Leu1266Val
NP_001070651.1:p.Leu1222Val
NP_001107854.1:p.Leu1266Val
NP_001305756.1:p.Leu1186Val
NP_001305758.1:p.Leu1174Val
NP_001305760.1:p.Leu1022Val
NP_001305761.1:p.Leu1233Val
NP_001350457.1:p.Leu1223Val
NP_001357333.1:p.Leu1222Val
NP_001357334.1:p.Leu1223Val
NP_001393592.1:p.Leu1265Val
NP_001393593.1:p.Leu1265Val
NP_001393594.1:p.Leu1222Val
NP_001393596.1:p.Leu1253Val
NP_001393597.1:p.Leu1252Val
NP_001393599.1:p.Leu1229Val
NP_001393600.1:p.Leu1219Val
NP_001393602.1:p.Leu1218Val
NP_001393604.1:p.Leu1217Val
NP_001393605.1:p.Leu1216Val
NP_001393606.1:p.Leu1203Val
NP_001393607.1:p.Leu1185Val
NP_001393608.1:p.Leu1173Val
NP_001393609.1:p.Leu1066Val
NP_001393610.1:p.Leu1069Val
NP_001393611.1:p.Leu1066Val
NP_001393612.1:p.Leu1066Val
NP_001393613.1:p.Leu1065Val
NP_001393614.1:p.Leu1023Val
NP_001393615.1:p.Leu1023Val
NP_001393616.1:p.Leu1022Val
NP_001393617.1:p.Leu1022Val
NP_001393618.1:p.Leu818Val
NP_001393619.1:p.Leu775Val
NP_001393620.1:p.Leu774Val
NP_001393621.1:p.Leu775Val
NP_001393622.1:p.Leu775Val
NP_001393623.1:p.Leu775Val
NP_001393624.1:p.Leu774Val
NP_001393625.1:p.Leu774Val
NP_001393626.1:p.Leu774Val
NP_001393627.1:p.Leu688Val
NP_066399.2:p.Leu1223Val
LRG_487t1:c.3796C>G
LRG_487:g.37475C>G
LRG_487p1:p.Leu1266Val
NC_000016.9:g.2131781C>G
NM_000548.3:c.3796C>G
NR_176225.1:n.3817C>G
NR_176226.1:n.3996C>G
NR_176227.1:n.3993C>G
NR_176228.1:n.3814C>G
NR_176229.1:n.3774C>G

Protein change:

L1022V

Molecular consequence:

NM_000548.5:c.3796C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.3664C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.3796C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.3556C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.3520C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.3064C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.3697C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.3667C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.3664C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.3667C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406663.1:c.3793C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406664.1:c.3793C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406665.1:c.3664C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406667.1:c.3757C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406668.1:c.3754C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406670.1:c.3685C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406671.1:c.3655C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406673.1:c.3652C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406675.1:c.3649C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406676.1:c.3646C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406677.1:c.3607C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406678.1:c.3553C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406679.1:c.3517C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406680.1:c.3196C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406681.1:c.3205C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406682.1:c.3196C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406683.1:c.3196C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406684.1:c.3193C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406685.1:c.3067C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406686.1:c.3067C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406687.1:c.3064C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406688.1:c.3064C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406689.1:c.2452C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406690.1:c.2323C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406691.1:c.2320C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406692.1:c.2323C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406693.1:c.2323C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406694.1:c.2323C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406695.1:c.2320C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406696.1:c.2320C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406697.1:c.2320C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406698.1:c.2062C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.3667C>G - 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
SCV004445815	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 21, 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

SCV004445815

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 21, 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, SCV004445815.1

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

Description

This variant has not been reported in the literature in individuals affected with TSC2-related conditions. 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: 1734981). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1266 of the TSC2 protein (p.Leu1266Val).

#	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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