NM_000368.5(TSC1):c.2841G>T (p.Arg947Ser) AND Tuberous sclerosis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 25, 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:: RCV000642030.7

Allele description [Variation Report for NM_000368.5(TSC1):c.2841G>T (p.Arg947Ser)]

NM_000368.5(TSC1):c.2841G>T (p.Arg947Ser)

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.2841G>T (p.Arg947Ser)

HGVS:

NC_000009.12:g.132897318C>A
NG_012386.1:g.52316G>T
NM_000368.5:c.2841G>TMANE SELECT
NM_001162426.2:c.2838G>T
NM_001162427.2:c.2688G>T
NM_001362177.2:c.2478G>T
NP_000359.1:p.Arg947Ser
NP_000359.1:p.Arg947Ser
NP_001155898.1:p.Arg946Ser
NP_001155899.1:p.Arg896Ser
NP_001349106.1:p.Arg826Ser
LRG_486t1:c.2841G>T
LRG_486:g.52316G>T
LRG_486p1:p.Arg947Ser
NC_000009.11:g.135772705C>A
NM_000368.4:c.2841G>T

Protein change:

R826S

Links:

dbSNP: rs1417111404

NCBI 1000 Genomes Browser:

rs1417111404

Molecular consequence:

NM_000368.5:c.2841G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.2838G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.2688G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.2478G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000763683	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 25, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29619247, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000763683

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 25, 2022)

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

Cardiac arrhythmia and neuroexcitability gene variants in resected brain tissue from patients with sudden unexpected death in epilepsy (SUDEP).

Friedman D, Kannan K, Faustin A, Shroff S, Thomas C, Heguy A, Serrano J, Snuderl M, Devinsky O.

NPJ Genom Med. 2018;3:9. doi: 10.1038/s41525-018-0048-5.

PubMed [citation]

PMID:: 29619247
PMCID:: PMC5869741

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000763683.5

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

Description

This variant is also known as R946S. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 534463). This missense change has been observed in individual(s) with epilepsy (PMID: 29619247). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 947 of the TSC1 protein (p.Arg947Ser).

#	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: Feb 14, 2024

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Relating variation to medicine