The p.S1723L variant (also known as c.5168C>T), located in coding exon 40 of the TSC2 gene, results from a C to T substitution at nucleotide position 5168. The serine at codon 1723 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.5168C>T (p.Ser1723Leu)
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)
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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.5168C>T (p.Ser1723Leu)
Variation ID: 2449978 Accession: VCV002449978.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2088234 (GRCh38) [ NCBI UCSC ] 16: 2138235 (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 15, 2023 May 1, 2024 Jan 27, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.5168C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Ser1723Leu missense NM_001077183.3:c.4967C>T NP_001070651.1:p.Ser1656Leu missense NM_001114382.3:c.5099C>T NP_001107854.1:p.Ser1700Leu missense NM_001318827.2:c.4859C>T NP_001305756.1:p.Ser1620Leu missense NM_001318829.2:c.4823C>T NP_001305758.1:p.Ser1608Leu missense NM_001318831.2:c.4436C>T NP_001305760.1:p.Ser1479Leu missense NM_001318832.2:c.5000C>T NP_001305761.1:p.Ser1667Leu missense NM_001363528.2:c.4970C>T NP_001350457.1:p.Ser1657Leu missense NM_001370404.1:c.5036C>T NP_001357333.1:p.Ser1679Leu missense NM_001370405.1:c.5032-5C>T intron variant NM_001406663.1:c.5165C>T NP_001393592.1:p.Ser1722Leu missense NM_001406664.1:c.5096C>T NP_001393593.1:p.Ser1699Leu missense NM_001406665.1:c.5090C>T NP_001393594.1:p.Ser1697Leu missense NM_001406667.1:c.5060C>T NP_001393596.1:p.Ser1687Leu missense NM_001406668.1:c.5057C>T NP_001393597.1:p.Ser1686Leu missense NM_001406670.1:c.4988C>T NP_001393599.1:p.Ser1663Leu missense NM_001406671.1:c.4958C>T NP_001393600.1:p.Ser1653Leu missense NM_001406673.1:c.4955C>T NP_001393602.1:p.Ser1652Leu missense NM_001406675.1:c.4952C>T NP_001393604.1:p.Ser1651Leu missense NM_001406676.1:c.4949C>T NP_001393605.1:p.Ser1650Leu missense NM_001406677.1:c.4910C>T NP_001393606.1:p.Ser1637Leu missense NM_001406678.1:c.4856C>T NP_001393607.1:p.Ser1619Leu missense NM_001406679.1:c.4820C>T NP_001393608.1:p.Ser1607Leu missense NM_001406680.1:c.4568C>T NP_001393609.1:p.Ser1523Leu missense NM_001406681.1:c.4508C>T NP_001393610.1:p.Ser1503Leu missense NM_001406682.1:c.4499C>T NP_001393611.1:p.Ser1500Leu missense NM_001406683.1:c.4499C>T NP_001393612.1:p.Ser1500Leu missense NM_001406684.1:c.4496C>T NP_001393613.1:p.Ser1499Leu missense NM_001406685.1:c.4370C>T NP_001393614.1:p.Ser1457Leu missense NM_001406686.1:c.4370C>T NP_001393615.1:p.Ser1457Leu missense NM_001406687.1:c.4367C>T NP_001393616.1:p.Ser1456Leu missense NM_001406688.1:c.4367C>T NP_001393617.1:p.Ser1456Leu missense NM_001406689.1:c.3755C>T NP_001393618.1:p.Ser1252Leu missense NM_001406690.1:c.3695C>T NP_001393619.1:p.Ser1232Leu missense NM_001406691.1:c.3692C>T NP_001393620.1:p.Ser1231Leu missense NM_001406692.1:c.3626C>T NP_001393621.1:p.Ser1209Leu missense NM_001406693.1:c.3626C>T NP_001393622.1:p.Ser1209Leu missense NM_001406694.1:c.3626C>T NP_001393623.1:p.Ser1209Leu missense NM_001406695.1:c.3623C>T NP_001393624.1:p.Ser1208Leu missense NM_001406696.1:c.3623C>T NP_001393625.1:p.Ser1208Leu missense NM_001406697.1:c.3623C>T NP_001393626.1:p.Ser1208Leu missense NM_001406698.1:c.3365C>T NP_001393627.1:p.Ser1122Leu missense NM_021055.3:c.5039C>T NP_066399.2:p.Ser1680Leu missense NR_176225.1:n.5120C>T non-coding transcript variant NR_176226.1:n.5368C>T non-coding transcript variant NR_176227.1:n.5296C>T non-coding transcript variant NR_176228.1:n.5117C>T non-coding transcript variant NR_176229.1:n.5042C>T non-coding transcript variant NC_000016.10:g.2088234C>T NC_000016.9:g.2138235C>T NG_005895.1:g.43929C>T NG_008617.1:g.54987G>A LRG_487:g.43929C>T LRG_487t1:c.5168C>T LRG_487p1:p.Ser1723Leu - Protein change
- S1209L, S1456L, S1457L, S1686L, S1697L, S1700L, S1723L, S1208L, S1608L, S1619L, S1650L, S1651L, S1656L, S1667L, S1679L, S1680L, S1231L, S1500L, S1503L, S1637L, S1699L, S1722L, S1122L, S1232L, S1252L, S1479L, S1499L, S1523L, S1607L, S1620L, S1652L, S1653L, S1657L, S1663L, S1687L
- Other names
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- Canonical SPDI
- NC_000016.10:2088233:C: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
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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Jan 27, 2023 | RCV003171311.2 |
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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Uncertain significance
(Jan 27, 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: SCV003861786.2
First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024 |
Comment:
The p.S1723L variant (also known as c.5168C>T), located in coding exon 40 of the TSC2 gene, results from a C to T substitution at nucleotide … (more)
The p.S1723L variant (also known as c.5168C>T), located in coding exon 40 of the TSC2 gene, results from a C to T substitution at nucleotide position 5168. The serine at codon 1723 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (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:
The p.S1723L variant (also known as c.5168C>T), located in coding exon 40 of the TSC2 gene, results from a C to T substitution at nucleotide position 5168. The serine at codon 1723 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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 May 01, 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.