NM_000548.5(TSC2):c.4633A>G (p.Ile1545Val) AND Tuberous sclerosis syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 4, 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:: RCV003998830.2

Allele description [Variation Report for NM_000548.5(TSC2):c.4633A>G (p.Ile1545Val)]

NM_000548.5(TSC2):c.4633A>G (p.Ile1545Val)

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.4633A>G (p.Ile1545Val)

HGVS:

NC_000016.10:g.2085293A>G
NG_005895.1:g.40988A>G
NM_000548.5:c.4633A>GMANE SELECT
NM_001077183.3:c.4432A>G
NM_001114382.3:c.4564A>G
NM_001318827.2:c.4324A>G
NM_001318829.2:c.4288A>G
NM_001318831.2:c.3901A>G
NM_001318832.2:c.4465A>G
NM_001363528.2:c.4435A>G
NM_001370404.1:c.4501A>G
NM_001370405.1:c.4504A>G
NM_021055.3:c.4504A>G
NP_000539.2:p.Ile1545Val
NP_001070651.1:p.Ile1478Val
NP_001107854.1:p.Ile1522Val
NP_001305756.1:p.Ile1442Val
NP_001305758.1:p.Ile1430Val
NP_001305760.1:p.Ile1301Val
NP_001305761.1:p.Ile1489Val
NP_001350457.1:p.Ile1479Val
NP_001357333.1:p.Ile1501Val
NP_001357334.1:p.Ile1502Val
NP_066399.2:p.Ile1502Val
LRG_487t1:c.4633A>G
LRG_487:g.40988A>G
NC_000016.9:g.2135294A>G
NM_000548.3:c.4633A>G

Protein change:

I1301V

Links:

dbSNP: rs878854109

NCBI 1000 Genomes Browser:

rs878854109

Molecular consequence:

NM_000548.5:c.4633A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.4432A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.4564A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.4324A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.4288A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.3901A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.4465A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.4435A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.4501A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.4504A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.4504A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Tuberous sclerosis syndrome (TSC)
Synonyms:: Tuberous sclerosis
Identifiers:: MONDO: MONDO:0001734; MedGen: C0041341; OMIM: PS191100

Recent activity

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endoribonuclease Dicer isoform 11 [Homo sapiens]
endoribonuclease Dicer isoform 11 [Homo sapiens]
gi|2074816303|ref|NP_001382628.1|

Protein
CD79A CD79a molecule [Bos taurus]
CD79A CD79a molecule [Bos taurus]
Gene ID:281674

Gene
281674[uid] AND (alive[prop]) (1)
Gene
B3glct [Dipodomys ordii]
B3glct [Dipodomys ordii]
Gene ID:105993895

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004833055	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (May 4, 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

SCV004833055

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(May 4, 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	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004833055.1

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

Description

This missense variant replaces isoleucine with valine at codon 1545 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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