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 TSC2 protein function. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1304 of the TSC2 protein (p.Ser1304Arg).
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.3912T>G (p.Ser1304Arg)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(1)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000548.5(TSC2):c.3912T>G (p.Ser1304Arg)
Variation ID: 3004157 Accession: VCV003004157.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2083723 (GRCh38) [ NCBI UCSC ] 16: 2133724 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 29, 2024 Feb 28, 2024 Jan 24, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.3912T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Ser1304Arg missense NM_001077183.3:c.3711T>G NP_001070651.1:p.Ser1237Arg missense NM_001114382.3:c.3843T>G NP_001107854.1:p.Ser1281Arg missense NM_001318827.2:c.3603T>G NP_001305756.1:p.Ser1201Arg missense NM_001318829.2:c.3567T>G NP_001305758.1:p.Ser1189Arg missense NM_001318831.2:c.3180T>G NP_001305760.1:p.Ser1060Arg missense NM_001318832.2:c.3744T>G NP_001305761.1:p.Ser1248Arg missense NM_001363528.2:c.3714T>G NP_001350457.1:p.Ser1238Arg missense NM_001370404.1:c.3780T>G NP_001357333.1:p.Ser1260Arg missense NM_001370405.1:c.3783T>G NP_001357334.1:p.Ser1261Arg missense NM_001406663.1:c.3909T>G NP_001393592.1:p.Ser1303Arg missense NM_001406664.1:c.3840T>G NP_001393593.1:p.Ser1280Arg missense NM_001406665.1:c.3834T>G NP_001393594.1:p.Ser1278Arg missense NM_001406667.1:c.3804T>G NP_001393596.1:p.Ser1268Arg missense NM_001406668.1:c.3801T>G NP_001393597.1:p.Ser1267Arg missense NM_001406670.1:c.3732T>G NP_001393599.1:p.Ser1244Arg missense NM_001406671.1:c.3702T>G NP_001393600.1:p.Ser1234Arg missense NM_001406673.1:c.3699T>G NP_001393602.1:p.Ser1233Arg missense NM_001406675.1:c.3696T>G NP_001393604.1:p.Ser1232Arg missense NM_001406676.1:c.3693T>G NP_001393605.1:p.Ser1231Arg missense NM_001406677.1:c.3654T>G NP_001393606.1:p.Ser1218Arg missense NM_001406678.1:c.3600T>G NP_001393607.1:p.Ser1200Arg missense NM_001406679.1:c.3564T>G NP_001393608.1:p.Ser1188Arg missense NM_001406680.1:c.3312T>G NP_001393609.1:p.Ser1104Arg missense NM_001406681.1:c.3252T>G NP_001393610.1:p.Ser1084Arg missense NM_001406682.1:c.3243T>G NP_001393611.1:p.Ser1081Arg missense NM_001406683.1:c.3243T>G NP_001393612.1:p.Ser1081Arg missense NM_001406684.1:c.3240T>G NP_001393613.1:p.Ser1080Arg missense NM_001406685.1:c.3114T>G NP_001393614.1:p.Ser1038Arg missense NM_001406686.1:c.3114T>G NP_001393615.1:p.Ser1038Arg missense NM_001406687.1:c.3111T>G NP_001393616.1:p.Ser1037Arg missense NM_001406688.1:c.3111T>G NP_001393617.1:p.Ser1037Arg missense NM_001406689.1:c.2499T>G NP_001393618.1:p.Ser833Arg missense NM_001406690.1:c.2439T>G NP_001393619.1:p.Ser813Arg missense NM_001406691.1:c.2436T>G NP_001393620.1:p.Ser812Arg missense NM_001406692.1:c.2370T>G NP_001393621.1:p.Ser790Arg missense NM_001406693.1:c.2370T>G NP_001393622.1:p.Ser790Arg missense NM_001406694.1:c.2370T>G NP_001393623.1:p.Ser790Arg missense NM_001406695.1:c.2367T>G NP_001393624.1:p.Ser789Arg missense NM_001406696.1:c.2367T>G NP_001393625.1:p.Ser789Arg missense NM_001406697.1:c.2367T>G NP_001393626.1:p.Ser789Arg missense NM_001406698.1:c.2109T>G NP_001393627.1:p.Ser703Arg missense NM_021055.3:c.3783T>G NP_066399.2:p.Ser1261Arg missense NR_176225.1:n.3864T>G non-coding transcript variant NR_176226.1:n.4112T>G non-coding transcript variant NR_176227.1:n.4040T>G non-coding transcript variant NR_176228.1:n.3861T>G non-coding transcript variant NR_176229.1:n.3821T>G non-coding transcript variant NC_000016.10:g.2083723T>G NC_000016.9:g.2133724T>G NG_005895.1:g.39418T>G LRG_487:g.39418T>G LRG_487t1:c.3912T>G LRG_487p1:p.Ser1304Arg - Protein change
- S1038R, S1080R, S1189R, S1232R, S1233R, S1234R, S1237R, S789R, S1188R, S1260R, S1278R, S790R, S812R, S1037R, S1081R, S1084R, S1104R, S1231R, S1238R, S1244R, S1248R, S1261R, S1268R, S703R, S813R, S1060R, S1200R, S1201R, S1218R, S1267R, S1280R, S1281R, S1303R, S1304R, S833R
- Other names
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- Canonical SPDI
- NC_000016.10:2083722:T:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10758 | 10957 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 24, 2023 | RCV003865796.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Uncertain significance
(Jan 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004666213.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Comment:
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 … (more)
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 TSC2 protein function. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1304 of the TSC2 protein (p.Ser1304Arg). (less)
|
Comment:
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
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 TSC2 protein function. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1304 of the TSC2 protein (p.Ser1304Arg).
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Sep 30, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.