NM_000548.5(TSC2):c.3170C>A (p.Thr1057Asn) AND Tuberous sclerosis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 13, 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:: RCV003778996.2

Allele description [Variation Report for NM_000548.5(TSC2):c.3170C>A (p.Thr1057Asn)]

NM_000548.5(TSC2):c.3170C>A (p.Thr1057Asn)

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.3170C>A (p.Thr1057Asn)

HGVS:

NC_000016.10:g.2079314C>A
NG_005895.1:g.35009C>A
NM_000548.5:c.3170C>AMANE SELECT
NM_001077183.3:c.3038C>A
NM_001114382.3:c.3170C>A
NM_001318827.2:c.2930C>A
NM_001318829.2:c.2894C>A
NM_001318831.2:c.2438C>A
NM_001318832.2:c.3071C>A
NM_001363528.2:c.3041C>A
NM_001370404.1:c.3038C>A
NM_001370405.1:c.3041C>A
NM_001406663.1:c.3167C>A
NM_001406664.1:c.3167C>A
NM_001406665.1:c.3038C>A
NM_001406667.1:c.3131C>A
NM_001406668.1:c.3128C>A
NM_001406670.1:c.3059C>A
NM_001406671.1:c.3029C>A
NM_001406673.1:c.3026C>A
NM_001406675.1:c.3023C>A
NM_001406676.1:c.3020C>A
NM_001406677.1:c.2981C>A
NM_001406678.1:c.2927C>A
NM_001406679.1:c.2891C>A
NM_001406680.1:c.2570C>A
NM_001406681.1:c.2579C>A
NM_001406682.1:c.2570C>A
NM_001406683.1:c.2570C>A
NM_001406684.1:c.2567C>A
NM_001406685.1:c.2441C>A
NM_001406686.1:c.2441C>A
NM_001406687.1:c.2438C>A
NM_001406688.1:c.2438C>A
NM_001406689.1:c.1826C>A
NM_001406690.1:c.1697C>A
NM_001406691.1:c.1694C>A
NM_001406692.1:c.1697C>A
NM_001406693.1:c.1697C>A
NM_001406694.1:c.1697C>A
NM_001406695.1:c.1694C>A
NM_001406696.1:c.1694C>A
NM_001406697.1:c.1694C>A
NM_001406698.1:c.1436C>A
NM_021055.3:c.3041C>A
NP_000539.2:p.Thr1057Asn
NP_000539.2:p.Thr1057Asn
NP_001070651.1:p.Thr1013Asn
NP_001107854.1:p.Thr1057Asn
NP_001305756.1:p.Thr977Asn
NP_001305758.1:p.Thr965Asn
NP_001305760.1:p.Thr813Asn
NP_001305761.1:p.Thr1024Asn
NP_001350457.1:p.Thr1014Asn
NP_001357333.1:p.Thr1013Asn
NP_001357334.1:p.Thr1014Asn
NP_001393592.1:p.Thr1056Asn
NP_001393593.1:p.Thr1056Asn
NP_001393594.1:p.Thr1013Asn
NP_001393596.1:p.Thr1044Asn
NP_001393597.1:p.Thr1043Asn
NP_001393599.1:p.Thr1020Asn
NP_001393600.1:p.Thr1010Asn
NP_001393602.1:p.Thr1009Asn
NP_001393604.1:p.Thr1008Asn
NP_001393605.1:p.Thr1007Asn
NP_001393606.1:p.Thr994Asn
NP_001393607.1:p.Thr976Asn
NP_001393608.1:p.Thr964Asn
NP_001393609.1:p.Thr857Asn
NP_001393610.1:p.Thr860Asn
NP_001393611.1:p.Thr857Asn
NP_001393612.1:p.Thr857Asn
NP_001393613.1:p.Thr856Asn
NP_001393614.1:p.Thr814Asn
NP_001393615.1:p.Thr814Asn
NP_001393616.1:p.Thr813Asn
NP_001393617.1:p.Thr813Asn
NP_001393618.1:p.Thr609Asn
NP_001393619.1:p.Thr566Asn
NP_001393620.1:p.Thr565Asn
NP_001393621.1:p.Thr566Asn
NP_001393622.1:p.Thr566Asn
NP_001393623.1:p.Thr566Asn
NP_001393624.1:p.Thr565Asn
NP_001393625.1:p.Thr565Asn
NP_001393626.1:p.Thr565Asn
NP_001393627.1:p.Thr479Asn
NP_066399.2:p.Thr1014Asn
LRG_487t1:c.3170C>A
LRG_487:g.35009C>A
LRG_487p1:p.Thr1057Asn
NC_000016.9:g.2129315C>A
NM_000548.3:c.3170C>A
NR_176225.1:n.3191C>A
NR_176226.1:n.3370C>A
NR_176227.1:n.3367C>A
NR_176228.1:n.3188C>A
NR_176229.1:n.3148C>A

Protein change:

T1007N

Molecular consequence:

NM_000548.5:c.3170C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.3038C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.3170C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.2930C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.2894C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.2438C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.3071C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.3041C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.3038C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.3041C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406663.1:c.3167C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406664.1:c.3167C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406665.1:c.3038C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406667.1:c.3131C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406668.1:c.3128C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406670.1:c.3059C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406671.1:c.3029C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406673.1:c.3026C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406675.1:c.3023C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406676.1:c.3020C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406677.1:c.2981C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406678.1:c.2927C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406679.1:c.2891C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406680.1:c.2570C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406681.1:c.2579C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406682.1:c.2570C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406683.1:c.2570C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406684.1:c.2567C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406685.1:c.2441C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406686.1:c.2441C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406687.1:c.2438C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406688.1:c.2438C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406689.1:c.1826C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406690.1:c.1697C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406691.1:c.1694C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406692.1:c.1697C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406693.1:c.1697C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406694.1:c.1697C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406695.1:c.1694C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406696.1:c.1694C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406697.1:c.1694C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406698.1:c.1436C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.3041C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_176225.1:n.3191C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176226.1:n.3370C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176227.1:n.3367C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176228.1:n.3188C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176229.1:n.3148C>A - 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

Recent activity

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Mus musculus ADP-ribosylation factor-like 2 binding protein (Arl2bp), transcript...
Mus musculus ADP-ribosylation factor-like 2 binding protein (Arl2bp), transcript variant 2, mRNA
gi|30842832|ref|NM_024269.2|

Nucleotide
RecName: Full=7SK snRNA methylphosphate capping enzyme; Short=MePCE
RecName: Full=7SK snRNA methylphosphate capping enzyme; Short=MePCE
gi|156631026|sp|Q8K3A9.2|MEPCE_MOUS

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004638245	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 13, 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

SCV004638245

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 13, 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, SCV004638245.1

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

Description

This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1057 of the TSC2 protein (p.Thr1057Asn). 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).

#	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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