This missense variant replaces glycine with arginine at codon 1787 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.5359G>C (p.Gly1787Arg)
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.
(2)
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
2
criteria provided, multiple submitters, no conflicts
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.5359G>C (p.Gly1787Arg)
Variation ID: 3075067 Accession: VCV003075067.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2088545 (GRCh38) [ NCBI UCSC ] 16: 2138546 (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 Apr 20, 2024 May 1, 2024 Dec 18, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.5359G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Gly1787Arg missense NM_001077183.3:c.5158G>C NP_001070651.1:p.Gly1720Arg missense NM_001114382.3:c.5290G>C NP_001107854.1:p.Gly1764Arg missense NM_001318827.2:c.5050G>C NP_001305756.1:p.Gly1684Arg missense NM_001318829.2:c.5014G>C NP_001305758.1:p.Gly1672Arg missense NM_001318831.2:c.4627G>C NP_001305760.1:p.Gly1543Arg missense NM_001318832.2:c.5191G>C NP_001305761.1:p.Gly1731Arg missense NM_001363528.2:c.5161G>C NP_001350457.1:p.Gly1721Arg missense NM_001370404.1:c.5227G>C NP_001357333.1:p.Gly1743Arg missense NM_001370405.1:c.5218G>C NP_001357334.1:p.Gly1740Arg missense NM_001406663.1:c.5356G>C NP_001393592.1:p.Gly1786Arg missense NM_001406664.1:c.5287G>C NP_001393593.1:p.Gly1763Arg missense NM_001406665.1:c.5281G>C NP_001393594.1:p.Gly1761Arg missense NM_001406667.1:c.5251G>C NP_001393596.1:p.Gly1751Arg missense NM_001406668.1:c.5248G>C NP_001393597.1:p.Gly1750Arg missense NM_001406670.1:c.5179G>C NP_001393599.1:p.Gly1727Arg missense NM_001406671.1:c.5149G>C NP_001393600.1:p.Gly1717Arg missense NM_001406673.1:c.5146G>C NP_001393602.1:p.Gly1716Arg missense NM_001406675.1:c.5143G>C NP_001393604.1:p.Gly1715Arg missense NM_001406676.1:c.5140G>C NP_001393605.1:p.Gly1714Arg missense NM_001406677.1:c.5101G>C NP_001393606.1:p.Gly1701Arg missense NM_001406678.1:c.5047G>C NP_001393607.1:p.Gly1683Arg missense NM_001406679.1:c.5011G>C NP_001393608.1:p.Gly1671Arg missense NM_001406680.1:c.4759G>C NP_001393609.1:p.Gly1587Arg missense NM_001406681.1:c.4699G>C NP_001393610.1:p.Gly1567Arg missense NM_001406682.1:c.4690G>C NP_001393611.1:p.Gly1564Arg missense NM_001406683.1:c.4690G>C NP_001393612.1:p.Gly1564Arg missense NM_001406684.1:c.4687G>C NP_001393613.1:p.Gly1563Arg missense NM_001406685.1:c.4561G>C NP_001393614.1:p.Gly1521Arg missense NM_001406686.1:c.4561G>C NP_001393615.1:p.Gly1521Arg missense NM_001406687.1:c.4558G>C NP_001393616.1:p.Gly1520Arg missense NM_001406688.1:c.4558G>C NP_001393617.1:p.Gly1520Arg missense NM_001406689.1:c.3946G>C NP_001393618.1:p.Gly1316Arg missense NM_001406690.1:c.3886G>C NP_001393619.1:p.Gly1296Arg missense NM_001406691.1:c.3883G>C NP_001393620.1:p.Gly1295Arg missense NM_001406692.1:c.3817G>C NP_001393621.1:p.Gly1273Arg missense NM_001406693.1:c.3817G>C NP_001393622.1:p.Gly1273Arg missense NM_001406694.1:c.3817G>C NP_001393623.1:p.Gly1273Arg missense NM_001406695.1:c.3814G>C NP_001393624.1:p.Gly1272Arg missense NM_001406696.1:c.3814G>C NP_001393625.1:p.Gly1272Arg missense NM_001406697.1:c.3814G>C NP_001393626.1:p.Gly1272Arg missense NM_001406698.1:c.3556G>C NP_001393627.1:p.Gly1186Arg missense NM_021055.3:c.5230G>C NP_066399.2:p.Gly1744Arg missense NR_176225.1:n.5311G>C non-coding transcript variant NR_176226.1:n.5559G>C non-coding transcript variant NR_176227.1:n.5487G>C non-coding transcript variant NR_176228.1:n.5308G>C non-coding transcript variant NR_176229.1:n.5233G>C non-coding transcript variant NC_000016.10:g.2088545G>C NC_000016.9:g.2138546G>C NG_005895.1:g.44240G>C NG_008617.1:g.54676C>G LRG_487:g.44240G>C LRG_487t1:c.5359G>C LRG_487p1:p.Gly1787Arg - Protein change
- G1186R, G1272R, G1273R, G1295R, G1296R, G1316R, G1520R, G1521R, G1543R, G1563R, G1564R, G1567R, G1587R, G1671R, G1672R, G1683R, G1684R, G1701R, G1714R, G1715R, G1716R, G1717R, G1720R, G1721R, G1727R, G1731R, G1740R, G1743R, G1744R, G1750R, G1751R, G1761R, G1763R, G1764R, G1786R, G1787R
- Other names
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- Canonical SPDI
- NC_000016.10:2088544:G:C
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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 |
10752 | 10951 | |
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
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Dec 18, 2023 | RCV004015593.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
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Nov 6, 2023 | RCV004371993.1 |
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
(Dec 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004838418.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This missense variant replaces glycine with arginine at codon 1787 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces glycine with arginine at codon 1787 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Nov 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV005036445.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The p.G1787R variant (also known as c.5359G>C), located in coding exon 41 of the TSC2 gene, results from a G to C substitution at nucleotide … (more)
The p.G1787R variant (also known as c.5359G>C), located in coding exon 41 of the TSC2 gene, results from a G to C substitution at nucleotide position 5359. The glycine at codon 1787 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The p.G1787R variant (also known as c.5359G>C), located in coding exon 41 of the TSC2 gene, results from a G to C substitution at nucleotide position 5359. The glycine at codon 1787 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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:
This missense variant replaces glycine with arginine at codon 1787 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
The p.G1787R variant (also known as c.5359G>C), located in coding exon 41 of the TSC2 gene, results from a G to C substitution at nucleotide position 5359. The glycine at codon 1787 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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 Jun 02, 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.