NM_000368.5(TSC1):c.1267G>A (p.Glu423Lys) AND Tuberous sclerosis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 20, 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:: RCV003614962.2

Allele description [Variation Report for NM_000368.5(TSC1):c.1267G>A (p.Glu423Lys)]

NM_000368.5(TSC1):c.1267G>A (p.Glu423Lys)

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.1267G>A (p.Glu423Lys)

HGVS:

NC_000009.12:g.132907367C>T
NG_012386.1:g.42267G>A
NM_000368.5:c.1267G>AMANE SELECT
NM_001162426.2:c.1264G>A
NM_001162427.2:c.1114G>A
NM_001362177.2:c.904G>A
NM_001406592.1:c.1267G>A
NM_001406593.1:c.1267G>A
NM_001406594.1:c.1267G>A
NM_001406595.1:c.1267G>A
NM_001406596.1:c.1267G>A
NM_001406597.1:c.1264G>A
NM_001406598.1:c.1264G>A
NM_001406599.1:c.1264G>A
NM_001406600.1:c.1264G>A
NM_001406601.1:c.1267G>A
NM_001406602.1:c.1267G>A
NM_001406603.1:c.1264G>A
NM_001406604.1:c.1264G>A
NM_001406605.1:c.1267G>A
NM_001406606.1:c.1267G>A
NM_001406607.1:c.1267G>A
NM_001406608.1:c.1264G>A
NM_001406609.1:c.1264G>A
NM_001406610.1:c.1114G>A
NM_001406611.1:c.1111G>A
NM_001406612.1:c.1111G>A
NM_001406613.1:c.1111G>A
NM_001406614.1:c.904G>A
NM_001406615.1:c.904G>A
NM_001406616.1:c.904G>A
NM_001406617.1:c.904G>A
NM_001406618.1:c.904G>A
NM_001406619.1:c.904G>A
NM_001406620.1:c.901G>A
NM_001406621.1:c.901G>A
NM_001406622.1:c.901G>A
NM_001406623.1:c.901G>A
NM_001406624.1:c.904G>A
NM_001406625.1:c.901G>A
NM_001406626.1:c.316G>A
NM_001406627.1:c.313G>A
NM_001406628.1:c.313G>A
NM_001406629.1:c.214G>A
NM_001406630.1:c.214G>A
NP_000359.1:p.Glu423Lys
NP_000359.1:p.Glu423Lys
NP_000359.1:p.Glu423Lys
NP_001155898.1:p.Glu422Lys
NP_001155899.1:p.Glu372Lys
NP_001349106.1:p.Glu302Lys
NP_001393521.1:p.Glu423Lys
NP_001393522.1:p.Glu423Lys
NP_001393523.1:p.Glu423Lys
NP_001393524.1:p.Glu423Lys
NP_001393525.1:p.Glu423Lys
NP_001393526.1:p.Glu422Lys
NP_001393527.1:p.Glu422Lys
NP_001393528.1:p.Glu422Lys
NP_001393529.1:p.Glu422Lys
NP_001393530.1:p.Glu423Lys
NP_001393531.1:p.Glu423Lys
NP_001393532.1:p.Glu422Lys
NP_001393533.1:p.Glu422Lys
NP_001393534.1:p.Glu423Lys
NP_001393535.1:p.Glu423Lys
NP_001393536.1:p.Glu423Lys
NP_001393537.1:p.Glu422Lys
NP_001393538.1:p.Glu422Lys
NP_001393539.1:p.Glu372Lys
NP_001393540.1:p.Glu371Lys
NP_001393541.1:p.Glu371Lys
NP_001393542.1:p.Glu371Lys
NP_001393543.1:p.Glu302Lys
NP_001393544.1:p.Glu302Lys
NP_001393545.1:p.Glu302Lys
NP_001393546.1:p.Glu302Lys
NP_001393547.1:p.Glu302Lys
NP_001393548.1:p.Glu302Lys
NP_001393549.1:p.Glu301Lys
NP_001393550.1:p.Glu301Lys
NP_001393551.1:p.Glu301Lys
NP_001393552.1:p.Glu301Lys
NP_001393553.1:p.Glu302Lys
NP_001393554.1:p.Glu301Lys
NP_001393555.1:p.Glu106Lys
NP_001393556.1:p.Glu105Lys
NP_001393557.1:p.Glu105Lys
NP_001393558.1:p.Glu72Lys
NP_001393559.1:p.Glu72Lys
LRG_486t1:c.1267G>A
LRG_486:g.42267G>A
LRG_486p1:p.Glu423Lys
NC_000009.11:g.135782754C>T
NM_000368.3:c.1267G>A
NM_000368.4:c.1267G>A
NR_176214.1:n.1484G>A
NR_176215.1:n.1484G>A
NR_176216.1:n.1351G>A
NR_176217.1:n.1481G>A
NR_176218.1:n.1484G>A

Protein change:

E105K

Molecular consequence:

NM_000368.5:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.1264G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406592.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406593.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406594.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406595.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406596.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406597.1:c.1264G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406598.1:c.1264G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406599.1:c.1264G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406600.1:c.1264G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406601.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406602.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406603.1:c.1264G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406604.1:c.1264G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406605.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406606.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406607.1:c.1267G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406608.1:c.1264G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406609.1:c.1264G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406610.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406611.1:c.1111G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406612.1:c.1111G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406613.1:c.1111G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406614.1:c.904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406615.1:c.904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406616.1:c.904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406617.1:c.904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406618.1:c.904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406619.1:c.904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406620.1:c.901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406621.1:c.901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406622.1:c.901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406623.1:c.901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406624.1:c.904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406625.1:c.901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406626.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406627.1:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406628.1:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406629.1:c.214G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406630.1:c.214G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_176214.1:n.1484G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176215.1:n.1484G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176216.1:n.1351G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176217.1:n.1481G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176218.1:n.1484G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004467960	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 20, 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

SCV004467960

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 20, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004467960.1

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 423 of the TSC1 protein (p.Glu423Lys). This variant has not been reported in the literature in individuals affected with TSC1-related conditions. 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. 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.

#	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: Sep 29, 2024

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