NM_000548.5(TSC2):c.4591G>T (p.Val1531Leu) AND Tuberous sclerosis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 27, 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:: RCV003627812.2

Allele description [Variation Report for NM_000548.5(TSC2):c.4591G>T (p.Val1531Leu)]

NM_000548.5(TSC2):c.4591G>T (p.Val1531Leu)

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.4591G>T (p.Val1531Leu)

HGVS:

NC_000016.10:g.2085251G>T
NG_005895.1:g.40946G>T
NM_000548.5:c.4591G>TMANE SELECT
NM_001077183.3:c.4390G>T
NM_001114382.3:c.4522G>T
NM_001318827.2:c.4282G>T
NM_001318829.2:c.4246G>T
NM_001318831.2:c.3859G>T
NM_001318832.2:c.4423G>T
NM_001363528.2:c.4393G>T
NM_001370404.1:c.4459G>T
NM_001370405.1:c.4462G>T
NM_001406663.1:c.4588G>T
NM_001406664.1:c.4519G>T
NM_001406665.1:c.4513G>T
NM_001406667.1:c.4483G>T
NM_001406668.1:c.4480G>T
NM_001406670.1:c.4411G>T
NM_001406671.1:c.4381G>T
NM_001406673.1:c.4378G>T
NM_001406675.1:c.4375G>T
NM_001406676.1:c.4372G>T
NM_001406677.1:c.4333G>T
NM_001406678.1:c.4279G>T
NM_001406679.1:c.4243G>T
NM_001406680.1:c.3991G>T
NM_001406681.1:c.3931G>T
NM_001406682.1:c.3922G>T
NM_001406683.1:c.3922G>T
NM_001406684.1:c.3919G>T
NM_001406685.1:c.3793G>T
NM_001406686.1:c.3793G>T
NM_001406687.1:c.3790G>T
NM_001406688.1:c.3790G>T
NM_001406689.1:c.3178G>T
NM_001406690.1:c.3118G>T
NM_001406691.1:c.3115G>T
NM_001406692.1:c.3049G>T
NM_001406693.1:c.3049G>T
NM_001406694.1:c.3049G>T
NM_001406695.1:c.3046G>T
NM_001406696.1:c.3046G>T
NM_001406697.1:c.3046G>T
NM_001406698.1:c.2788G>T
NM_021055.3:c.4462G>T
NP_000539.2:p.Val1531Leu
NP_000539.2:p.Val1531Leu
NP_001070651.1:p.Val1464Leu
NP_001107854.1:p.Val1508Leu
NP_001305756.1:p.Val1428Leu
NP_001305758.1:p.Val1416Leu
NP_001305760.1:p.Val1287Leu
NP_001305761.1:p.Val1475Leu
NP_001350457.1:p.Val1465Leu
NP_001357333.1:p.Val1487Leu
NP_001357334.1:p.Val1488Leu
NP_001393592.1:p.Val1530Leu
NP_001393593.1:p.Val1507Leu
NP_001393594.1:p.Val1505Leu
NP_001393596.1:p.Val1495Leu
NP_001393597.1:p.Val1494Leu
NP_001393599.1:p.Val1471Leu
NP_001393600.1:p.Val1461Leu
NP_001393602.1:p.Val1460Leu
NP_001393604.1:p.Val1459Leu
NP_001393605.1:p.Val1458Leu
NP_001393606.1:p.Val1445Leu
NP_001393607.1:p.Val1427Leu
NP_001393608.1:p.Val1415Leu
NP_001393609.1:p.Val1331Leu
NP_001393610.1:p.Val1311Leu
NP_001393611.1:p.Val1308Leu
NP_001393612.1:p.Val1308Leu
NP_001393613.1:p.Val1307Leu
NP_001393614.1:p.Val1265Leu
NP_001393615.1:p.Val1265Leu
NP_001393616.1:p.Val1264Leu
NP_001393617.1:p.Val1264Leu
NP_001393618.1:p.Val1060Leu
NP_001393619.1:p.Val1040Leu
NP_001393620.1:p.Val1039Leu
NP_001393621.1:p.Val1017Leu
NP_001393622.1:p.Val1017Leu
NP_001393623.1:p.Val1017Leu
NP_001393624.1:p.Val1016Leu
NP_001393625.1:p.Val1016Leu
NP_001393626.1:p.Val1016Leu
NP_001393627.1:p.Val930Leu
NP_066399.2:p.Val1488Leu
LRG_487t1:c.4591G>T
LRG_487:g.40946G>T
LRG_487p1:p.Val1531Leu
NC_000016.9:g.2135252G>T
NM_000548.3:c.4591G>T
NR_176225.1:n.4543G>T
NR_176226.1:n.4791G>T
NR_176227.1:n.4719G>T
NR_176228.1:n.4540G>T
NR_176229.1:n.4500G>T

Protein change:

V1016L

Molecular consequence:

NM_000548.5:c.4591G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.4390G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.4522G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.4282G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.4246G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.3859G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.4423G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.4393G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.4459G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.4462G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406663.1:c.4588G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406664.1:c.4519G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406665.1:c.4513G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406667.1:c.4483G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406668.1:c.4480G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406670.1:c.4411G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406671.1:c.4381G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406673.1:c.4378G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406675.1:c.4375G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406676.1:c.4372G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406677.1:c.4333G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406678.1:c.4279G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406679.1:c.4243G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406680.1:c.3991G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406681.1:c.3931G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406682.1:c.3922G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406683.1:c.3922G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406684.1:c.3919G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406685.1:c.3793G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406686.1:c.3793G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406687.1:c.3790G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406688.1:c.3790G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406689.1:c.3178G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406690.1:c.3118G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406691.1:c.3115G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406692.1:c.3049G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406693.1:c.3049G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406694.1:c.3049G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406695.1:c.3046G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406696.1:c.3046G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406697.1:c.3046G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406698.1:c.2788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.4462G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_176225.1:n.4543G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176226.1:n.4791G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176227.1:n.4719G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176228.1:n.4540G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176229.1:n.4500G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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V-type proton ATPase subunit G 3 [Mus musculus]
V-type proton ATPase subunit G 3 [Mus musculus]
gi|28893577|ref|NP_796371.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004407824	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 27, 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

SCV004407824

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 27, 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, SCV004407824.1

#	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 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 valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1531 of the TSC2 protein (p.Val1531Leu).

#	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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