NM_000548.5(TSC2):c.1828A>C (p.Ile610Leu) AND Tuberous sclerosis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 18, 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:: RCV003100868.3

Allele description [Variation Report for NM_000548.5(TSC2):c.1828A>C (p.Ile610Leu)]

NM_000548.5(TSC2):c.1828A>C (p.Ile610Leu)

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.1828A>C (p.Ile610Leu)

HGVS:

NC_000016.10:g.2070567A>C
NG_005895.1:g.26262A>C
NM_000548.5:c.1828A>CMANE SELECT
NM_001077183.3:c.1828A>C
NM_001114382.3:c.1828A>C
NM_001318827.2:c.1717A>C
NM_001318829.2:c.1681A>C
NM_001318831.2:c.1228A>C
NM_001318832.2:c.1861A>C
NM_001363528.2:c.1828A>C
NM_001370404.1:c.1828A>C
NM_001370405.1:c.1828A>C
NM_001406663.1:c.1828A>C
NM_001406664.1:c.1828A>C
NM_001406665.1:c.1828A>C
NM_001406667.1:c.1918A>C
NM_001406668.1:c.1918A>C
NM_001406670.1:c.1717A>C
NM_001406671.1:c.1816A>C
NM_001406673.1:c.1816A>C
NM_001406675.1:c.1681A>C
NM_001406676.1:c.1681A>C
NM_001406677.1:c.1771A>C
NM_001406678.1:c.1717A>C
NM_001406679.1:c.1681A>C
NM_001406680.1:c.1228A>C
NM_001406681.1:c.1366A>C
NM_001406682.1:c.1228A>C
NM_001406683.1:c.1228A>C
NM_001406684.1:c.1228A>C
NM_001406685.1:c.1228A>C
NM_001406686.1:c.1228A>C
NM_001406687.1:c.1228A>C
NM_001406688.1:c.1228A>C
NM_001406689.1:c.484A>C
NM_001406690.1:c.484A>C
NM_001406691.1:c.484A>C
NM_001406692.1:c.484A>C
NM_001406693.1:c.484A>C
NM_001406694.1:c.484A>C
NM_001406695.1:c.484A>C
NM_001406696.1:c.484A>C
NM_001406697.1:c.484A>C
NM_001406698.1:c.226A>C
NM_021055.3:c.1828A>C
NP_000539.2:p.Ile610Leu
NP_000539.2:p.Ile610Leu
NP_001070651.1:p.Ile610Leu
NP_001107854.1:p.Ile610Leu
NP_001305756.1:p.Ile573Leu
NP_001305758.1:p.Ile561Leu
NP_001305760.1:p.Ile410Leu
NP_001305761.1:p.Ile621Leu
NP_001350457.1:p.Ile610Leu
NP_001357333.1:p.Ile610Leu
NP_001357334.1:p.Ile610Leu
NP_001393592.1:p.Ile610Leu
NP_001393593.1:p.Ile610Leu
NP_001393594.1:p.Ile610Leu
NP_001393596.1:p.Ile640Leu
NP_001393597.1:p.Ile640Leu
NP_001393599.1:p.Ile573Leu
NP_001393600.1:p.Ile606Leu
NP_001393602.1:p.Ile606Leu
NP_001393604.1:p.Ile561Leu
NP_001393605.1:p.Ile561Leu
NP_001393606.1:p.Ile591Leu
NP_001393607.1:p.Ile573Leu
NP_001393608.1:p.Ile561Leu
NP_001393609.1:p.Ile410Leu
NP_001393610.1:p.Ile456Leu
NP_001393611.1:p.Ile410Leu
NP_001393612.1:p.Ile410Leu
NP_001393613.1:p.Ile410Leu
NP_001393614.1:p.Ile410Leu
NP_001393615.1:p.Ile410Leu
NP_001393616.1:p.Ile410Leu
NP_001393617.1:p.Ile410Leu
NP_001393618.1:p.Ile162Leu
NP_001393619.1:p.Ile162Leu
NP_001393620.1:p.Ile162Leu
NP_001393621.1:p.Ile162Leu
NP_001393622.1:p.Ile162Leu
NP_001393623.1:p.Ile162Leu
NP_001393624.1:p.Ile162Leu
NP_001393625.1:p.Ile162Leu
NP_001393626.1:p.Ile162Leu
NP_001393627.1:p.Ile76Leu
NP_066399.2:p.Ile610Leu
LRG_487t1:c.1828A>C
LRG_487:g.26262A>C
LRG_487p1:p.Ile610Leu
NC_000016.9:g.2120568A>C
NM_000548.3:c.1828A>C
NR_176225.1:n.1938A>C
NR_176226.1:n.2157A>C
NR_176227.1:n.2157A>C
NR_176228.1:n.1938A>C
NR_176229.1:n.1938A>C

Protein change:

I162L

Molecular consequence:

NM_000548.5:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.1717A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.1681A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.1228A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.1861A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406663.1:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406664.1:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406665.1:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406667.1:c.1918A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406668.1:c.1918A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406670.1:c.1717A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406671.1:c.1816A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406673.1:c.1816A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406675.1:c.1681A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406676.1:c.1681A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406677.1:c.1771A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406678.1:c.1717A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406679.1:c.1681A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406680.1:c.1228A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406681.1:c.1366A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406682.1:c.1228A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406683.1:c.1228A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406684.1:c.1228A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406685.1:c.1228A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406686.1:c.1228A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406687.1:c.1228A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406688.1:c.1228A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406689.1:c.484A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406690.1:c.484A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406691.1:c.484A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406692.1:c.484A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406693.1:c.484A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406694.1:c.484A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406695.1:c.484A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406696.1:c.484A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406697.1:c.484A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406698.1:c.226A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.1828A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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disintegrin and metalloproteinase domain-containing protein 29 preproprotein [Ho...
disintegrin and metalloproteinase domain-containing protein 29 preproprotein [Homo sapiens]
gi|195232763|ref|NP_001124177.1|

Protein
disintegrin and metalloproteinase domain-containing protein 29 isoform X1 [Homo ...
disintegrin and metalloproteinase domain-containing protein 29 isoform X1 [Homo sapiens]
gi|2462594665|ref|XP_054204790.1|

Protein
Saccharomyces cerevisiae S288C Mid1p (MID1), partial mRNA
Saccharomyces cerevisiae S288C Mid1p (MID1), partial mRNA
gi|296147488|ref|NM_001183129.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002991805	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 18, 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

SCV002991805

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 18, 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, SCV002991805.2

#	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. 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 isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 610 of the TSC2 protein (p.Ile610Leu).

#	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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