NM_000368.5(TSC1):c.607T>G (p.Leu203Val) AND Tuberous sclerosis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 19, 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:: RCV003614005.2

Allele description [Variation Report for NM_000368.5(TSC1):c.607T>G (p.Leu203Val)]

NM_000368.5(TSC1):c.607T>G (p.Leu203Val)

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.607T>G (p.Leu203Val)

HGVS:

NC_000009.12:g.132921875A>C
NG_012386.1:g.27759T>G
NM_000368.5:c.607T>GMANE SELECT
NM_001162426.2:c.607T>G
NM_001162427.2:c.454T>G
NM_001362177.2:c.244T>G
NM_001406592.1:c.607T>G
NM_001406593.1:c.607T>G
NM_001406594.1:c.607T>G
NM_001406595.1:c.607T>G
NM_001406596.1:c.607T>G
NM_001406597.1:c.607T>G
NM_001406598.1:c.607T>G
NM_001406599.1:c.607T>G
NM_001406600.1:c.607T>G
NM_001406601.1:c.607T>G
NM_001406602.1:c.607T>G
NM_001406603.1:c.607T>G
NM_001406604.1:c.607T>G
NM_001406605.1:c.607T>G
NM_001406606.1:c.607T>G
NM_001406607.1:c.607T>G
NM_001406608.1:c.607T>G
NM_001406609.1:c.607T>G
NM_001406610.1:c.454T>G
NM_001406611.1:c.454T>G
NM_001406612.1:c.454T>G
NM_001406613.1:c.454T>G
NM_001406614.1:c.244T>G
NM_001406615.1:c.244T>G
NM_001406616.1:c.244T>G
NM_001406617.1:c.244T>G
NM_001406618.1:c.244T>G
NM_001406619.1:c.244T>G
NM_001406620.1:c.244T>G
NM_001406621.1:c.244T>G
NM_001406622.1:c.244T>G
NM_001406623.1:c.244T>G
NM_001406624.1:c.244T>G
NM_001406625.1:c.244T>G
NM_001406626.1:c.-271T>G
NM_001406627.1:c.-271T>G
NM_001406628.1:c.-271T>G
NM_001406629.1:c.-413T>G
NM_001406630.1:c.-487T>G
NP_000359.1:p.Leu203Val
NP_000359.1:p.Leu203Val
NP_000359.1:p.Leu203Val
NP_001155898.1:p.Leu203Val
NP_001155899.1:p.Leu152Val
NP_001349106.1:p.Leu82Val
NP_001393521.1:p.Leu203Val
NP_001393522.1:p.Leu203Val
NP_001393523.1:p.Leu203Val
NP_001393524.1:p.Leu203Val
NP_001393525.1:p.Leu203Val
NP_001393526.1:p.Leu203Val
NP_001393527.1:p.Leu203Val
NP_001393528.1:p.Leu203Val
NP_001393529.1:p.Leu203Val
NP_001393530.1:p.Leu203Val
NP_001393531.1:p.Leu203Val
NP_001393532.1:p.Leu203Val
NP_001393533.1:p.Leu203Val
NP_001393534.1:p.Leu203Val
NP_001393535.1:p.Leu203Val
NP_001393536.1:p.Leu203Val
NP_001393537.1:p.Leu203Val
NP_001393538.1:p.Leu203Val
NP_001393539.1:p.Leu152Val
NP_001393540.1:p.Leu152Val
NP_001393541.1:p.Leu152Val
NP_001393542.1:p.Leu152Val
NP_001393543.1:p.Leu82Val
NP_001393544.1:p.Leu82Val
NP_001393545.1:p.Leu82Val
NP_001393546.1:p.Leu82Val
NP_001393547.1:p.Leu82Val
NP_001393548.1:p.Leu82Val
NP_001393549.1:p.Leu82Val
NP_001393550.1:p.Leu82Val
NP_001393551.1:p.Leu82Val
NP_001393552.1:p.Leu82Val
NP_001393553.1:p.Leu82Val
NP_001393554.1:p.Leu82Val
LRG_486t1:c.607T>G
LRG_486:g.27759T>G
LRG_486p1:p.Leu203Val
NC_000009.11:g.135797262A>C
NM_000368.3:c.607T>G
NM_000368.4:c.607T>G
NR_176214.1:n.824T>G
NR_176215.1:n.824T>G
NR_176216.1:n.691T>G
NR_176217.1:n.824T>G
NR_176218.1:n.824T>G

Protein change:

L152V

Molecular consequence:

NM_001406626.1:c.-271T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406627.1:c.-271T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406628.1:c.-271T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406629.1:c.-413T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406630.1:c.-487T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000368.5:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.454T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406592.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406593.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406594.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406595.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406596.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406597.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406598.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406599.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406600.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406601.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406602.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406603.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406604.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406605.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406606.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406607.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406608.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406609.1:c.607T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406610.1:c.454T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406611.1:c.454T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406612.1:c.454T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406613.1:c.454T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406614.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406615.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406616.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406617.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406618.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406619.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406620.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406621.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406622.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406623.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406624.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406625.1:c.244T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_176214.1:n.824T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176215.1:n.824T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176216.1:n.691T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176217.1:n.824T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176218.1:n.824T>G - 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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Mus musculus paired immunoglobin-like type 2 receptor alpha, mRNA (cDNA clone MG...
Mus musculus paired immunoglobin-like type 2 receptor alpha, mRNA (cDNA clone MGC:144436 IMAGE:40102015), complete cds
gi|115527703|gb|BC115565.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004433929	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 19, 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

SCV004433929

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 19, 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, SCV004433929.1

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 203 of the TSC1 protein (p.Leu203Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC1-related conditions. 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 95%. 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: Sep 29, 2024

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