ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.5321G>T (p.Ser1774Ile)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000548.5(TSC2):c.5321G>T (p.Ser1774Ile)
Variation ID: 1719840 Accession: VCV001719840.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2088507 (GRCh38) [ NCBI UCSC ] 16: 2138508 (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 Nov 5, 2022 May 1, 2024 Jun 9, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.5321G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Ser1774Ile missense NM_001077183.3:c.5120G>T NP_001070651.1:p.Ser1707Ile missense NM_001114382.3:c.5252G>T NP_001107854.1:p.Ser1751Ile missense NM_001318827.2:c.5012G>T NP_001305756.1:p.Ser1671Ile missense NM_001318829.2:c.4976G>T NP_001305758.1:p.Ser1659Ile missense NM_001318831.2:c.4589G>T NP_001305760.1:p.Ser1530Ile missense NM_001318832.2:c.5153G>T NP_001305761.1:p.Ser1718Ile missense NM_001363528.2:c.5123G>T NP_001350457.1:p.Ser1708Ile missense NM_001370404.1:c.5189G>T NP_001357333.1:p.Ser1730Ile missense NM_001370405.1:c.5180G>T NP_001357334.1:p.Ser1727Ile missense NM_001406663.1:c.5318G>T NP_001393592.1:p.Ser1773Ile missense NM_001406664.1:c.5249G>T NP_001393593.1:p.Ser1750Ile missense NM_001406665.1:c.5243G>T NP_001393594.1:p.Ser1748Ile missense NM_001406667.1:c.5213G>T NP_001393596.1:p.Ser1738Ile missense NM_001406668.1:c.5210G>T NP_001393597.1:p.Ser1737Ile missense NM_001406670.1:c.5141G>T NP_001393599.1:p.Ser1714Ile missense NM_001406671.1:c.5111G>T NP_001393600.1:p.Ser1704Ile missense NM_001406673.1:c.5108G>T NP_001393602.1:p.Ser1703Ile missense NM_001406675.1:c.5105G>T NP_001393604.1:p.Ser1702Ile missense NM_001406676.1:c.5102G>T NP_001393605.1:p.Ser1701Ile missense NM_001406677.1:c.5063G>T NP_001393606.1:p.Ser1688Ile missense NM_001406678.1:c.5009G>T NP_001393607.1:p.Ser1670Ile missense NM_001406679.1:c.4973G>T NP_001393608.1:p.Ser1658Ile missense NM_001406680.1:c.4721G>T NP_001393609.1:p.Ser1574Ile missense NM_001406681.1:c.4661G>T NP_001393610.1:p.Ser1554Ile missense NM_001406682.1:c.4652G>T NP_001393611.1:p.Ser1551Ile missense NM_001406683.1:c.4652G>T NP_001393612.1:p.Ser1551Ile missense NM_001406684.1:c.4649G>T NP_001393613.1:p.Ser1550Ile missense NM_001406685.1:c.4523G>T NP_001393614.1:p.Ser1508Ile missense NM_001406686.1:c.4523G>T NP_001393615.1:p.Ser1508Ile missense NM_001406687.1:c.4520G>T NP_001393616.1:p.Ser1507Ile missense NM_001406688.1:c.4520G>T NP_001393617.1:p.Ser1507Ile missense NM_001406689.1:c.3908G>T NP_001393618.1:p.Ser1303Ile missense NM_001406690.1:c.3848G>T NP_001393619.1:p.Ser1283Ile missense NM_001406691.1:c.3845G>T NP_001393620.1:p.Ser1282Ile missense NM_001406692.1:c.3779G>T NP_001393621.1:p.Ser1260Ile missense NM_001406693.1:c.3779G>T NP_001393622.1:p.Ser1260Ile missense NM_001406694.1:c.3779G>T NP_001393623.1:p.Ser1260Ile missense NM_001406695.1:c.3776G>T NP_001393624.1:p.Ser1259Ile missense NM_001406696.1:c.3776G>T NP_001393625.1:p.Ser1259Ile missense NM_001406697.1:c.3776G>T NP_001393626.1:p.Ser1259Ile missense NM_001406698.1:c.3518G>T NP_001393627.1:p.Ser1173Ile missense NM_021055.3:c.5192G>T NP_066399.2:p.Ser1731Ile missense NR_176225.1:n.5273G>T NR_176226.1:n.5521G>T NR_176227.1:n.5449G>T NR_176228.1:n.5270G>T NR_176229.1:n.5195G>T NC_000016.10:g.2088507G>T NC_000016.9:g.2138508G>T NG_005895.1:g.44202G>T NG_008617.1:g.54714C>A LRG_487:g.44202G>T LRG_487t1:c.5321G>T LRG_487p1:p.Ser1774Ile - Protein change
- S1173I, S1259I, S1260I, S1282I, S1283I, S1303I, S1507I, S1508I, S1530I, S1550I, S1551I, S1554I, S1574I, S1658I, S1659I, S1670I, S1671I, S1688I, S1701I, S1702I, S1703I, S1704I, S1707I, S1708I, S1714I, S1718I, S1727I, S1730I, S1731I, S1737I, S1738I, S1748I, S1750I, S1751I, S1773I, S1774I
- Other names
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- Canonical SPDI
- NC_000016.10:2088506:G:T
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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
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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
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
10739 | 10936 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (1) |
criteria provided, single submitter
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Sep 20, 2022 | RCV002304016.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jun 9, 2023 | RCV003308117.2 |
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
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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
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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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Uncertain significance
(Sep 20, 2022)
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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: SCV002591681.3
First in ClinVar: Nov 05, 2022 Last updated: Feb 20, 2024 |
Comment:
RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). In summary, the … (more)
RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1774 of the TSC2 protein (p.Ser1774Ile). (less)
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Uncertain significance
(Jun 09, 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: SCV003998695.2
First in ClinVar: Jul 08, 2023 Last updated: May 01, 2024 |
Comment:
The p.S1774I variant (also known as c.5321G>T), located in coding exon 41 of the TSC2 gene, results from a G to T substitution at nucleotide … (more)
The p.S1774I variant (also known as c.5321G>T), located in coding exon 41 of the TSC2 gene, results from a G to T substitution at nucleotide position 5321. The serine at codon 1774 is replaced by isoleucine, 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)
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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. |
Citations for germline classification of this variant
HelpThere 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 29, 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.