NM_000548.5(TSC2):c.2437G>A (p.Val813Met) AND Tuberous sclerosis syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 3, 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:: RCV003999270.2

Allele description [Variation Report for NM_000548.5(TSC2):c.2437G>A (p.Val813Met)]

NM_000548.5(TSC2):c.2437G>A (p.Val813Met)

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.2437G>A (p.Val813Met)

HGVS:

NC_000016.10:g.2074281G>A
NG_005895.1:g.29976G>A
NM_000548.5:c.2437G>AMANE SELECT
NM_001077183.3:c.2437G>A
NM_001114382.3:c.2437G>A
NM_001318827.2:c.2326G>A
NM_001318829.2:c.2290G>A
NM_001318831.2:c.1837G>A
NM_001318832.2:c.2470G>A
NM_001363528.2:c.2437G>A
NM_001370404.1:c.2437G>A
NM_001370405.1:c.2437G>A
NM_021055.3:c.2437G>A
NP_000539.2:p.Val813Met
NP_001070651.1:p.Val813Met
NP_001107854.1:p.Val813Met
NP_001305756.1:p.Val776Met
NP_001305758.1:p.Val764Met
NP_001305760.1:p.Val613Met
NP_001305761.1:p.Val824Met
NP_001350457.1:p.Val813Met
NP_001357333.1:p.Val813Met
NP_001357334.1:p.Val813Met
NP_066399.2:p.Val813Met
LRG_487t1:c.2437G>A
LRG_487:g.29976G>A
NC_000016.9:g.2124282G>A
NM_000548.3:c.2437G>A
NM_000548.4:c.2437G>A

Protein change:

V613M

Links:

dbSNP: rs375030314

NCBI 1000 Genomes Browser:

rs375030314

Molecular consequence:

NM_000548.5:c.2437G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.2437G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.2437G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.2326G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.2290G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.1837G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.2470G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.2437G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.2437G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.2437G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.2437G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004820505	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Apr 3, 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

SCV004820505

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Apr 3, 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, SCV004820505.1

#	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 valine with methionine at codon 813 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 been identified in 3/250560 chromosomes 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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