NM_000368.5(TSC1):c.2144G>A (p.Arg715Gln) AND Tuberous sclerosis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 3, 2024
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:: RCV001057359.5

Allele description [Variation Report for NM_000368.5(TSC1):c.2144G>A (p.Arg715Gln)]

NM_000368.5(TSC1):c.2144G>A (p.Arg715Gln)

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.2144G>A (p.Arg715Gln)

HGVS:

NC_000009.12:g.132903715C>T
NG_012386.1:g.45919G>A
NM_000368.5:c.2144G>AMANE SELECT
NM_001162426.2:c.2141G>A
NM_001162427.2:c.1991G>A
NM_001362177.2:c.1781G>A
NP_000359.1:p.Arg715Gln
NP_001155898.1:p.Arg714Gln
NP_001155899.1:p.Arg664Gln
NP_001349106.1:p.Arg594Gln
LRG_486t1:c.2144G>A
LRG_486:g.45919G>A
NC_000009.11:g.135779102C>T
NM_000368.4:c.2144G>A

Protein change:

R594Q

Links:

dbSNP: rs986350787

NCBI 1000 Genomes Browser:

rs986350787

Molecular consequence:

NM_000368.5:c.2144G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.2141G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.1991G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.1781G>A - 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

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PREDICTED: Homo sapiens metadherin (MTDH), transcript variant X1, mRNA
PREDICTED: Homo sapiens metadherin (MTDH), transcript variant X1, mRNA
gi|2217373747|ref|XM_011517368.3|

Nucleotide
PREDICTED: Homo sapiens metadherin (MTDH), transcript variant X5, mRNA
PREDICTED: Homo sapiens metadherin (MTDH), transcript variant X5, mRNA
gi|2217373752|ref|XM_017013968.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001221846	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 3, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35571021, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001221846

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 3, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Genetic and Phenotype Analysis of a Chinese Cohort of Infants and Children With Epilepsy.

Chuan Z, Ruikun C, Qian L, Shiyue M, Shengju H, Yong Y, Haibo L, Neng X, Yong Z, Huiqin X, Weijia W, Ling H, Bingbo Z, Zhang Q, Yan W, Zongfu C, Xu M.

Front Genet. 2022;13:869210. doi: 10.3389/fgene.2022.869210.

PubMed [citation]

PMID:: 35571021
PMCID:: PMC9091957

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, SCV001221846.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 715 of the TSC1 protein (p.Arg715Gln). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with epilepsy (PMID: 35571021). ClinVar contains an entry for this variant (Variation ID: 852697). 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 with a negative predictive value of 80%. 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.

#	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: Oct 8, 2024

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