NM_000368.5(TSC1):c.1988A>T (p.Glu663Val) AND Tuberous sclerosis 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 28, 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:: RCV001037895.7

Allele description

NM_000368.5(TSC1):c.1988A>T (p.Glu663Val)

Gene:

TSC1:TSC complex subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.13

Genomic location:

Preferred name:

NM_000368.5(TSC1):c.1988A>T (p.Glu663Val)

HGVS:

NC_000009.12:g.132905590T>A
NG_012386.1:g.44044A>T
NM_000368.5:c.1988A>TMANE SELECT
NM_001162426.2:c.1985A>T
NM_001162427.2:c.1835A>T
NM_001362177.2:c.1625A>T
NP_000359.1:p.Glu663Val
NP_001155898.1:p.Glu662Val
NP_001155899.1:p.Glu612Val
NP_001349106.1:p.Glu542Val
LRG_486t1:c.1988A>T
LRG_486:g.44044A>T
NC_000009.11:g.135780977T>A
NM_000368.4:c.1988A>T

Protein change:

E542V

Links:

dbSNP: rs1845605103

NCBI 1000 Genomes Browser:

rs1845605103

Molecular consequence:

NM_000368.5:c.1988A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.1985A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.1835A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.1625A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Tuberous sclerosis 1 (TSC1)
Identifiers:: MONDO: MONDO:0008612; MedGen: C1854465; Orphanet: 805; OMIM: 191100

Recent activity

Clear Turn Off Turn On

MULTISPECIES: hypothetical protein [Enterococcus]
MULTISPECIES: hypothetical protein [Enterococcus]
gi|498395400|ref|WP_010708982.1|

Protein
MULTISPECIES: hypothetical protein [Bacillota]
MULTISPECIES: hypothetical protein [Bacillota]
gi|1120478708|ref|WP_073340404.1|

Protein
ArdC-like ssDNA-binding domain-containing protein [Enterococcus faecalis]
ArdC-like ssDNA-binding domain-containing protein [Enterococcus faecalis]
gi|2743190170|ref|WP_349516383.1|

Protein
Hypocrea sp. 2F 18S ribosomal RNA gene, partial sequence
Hypocrea sp. 2F 18S ribosomal RNA gene, partial sequence
gi|224831272|gb|FJ716243.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001201330	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 28, 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

SCV001201330

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 28, 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	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 Invitae, SCV001201330.5

#	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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 TSC1 protein function. ClinVar contains an entry for this variant (Variation ID: 836707). This variant has not been reported in the literature in individuals affected with TSC1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 663 of the TSC1 protein (p.Glu663Val).

#	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: May 7, 2024

ClinVar

Relating variation to medicine