TSC is a disorder that causes hamartomas in multiple organs (e.g., brain, eyes, skin, kidneys). The pathogenesis of TSC involves changes in cellular proliferation and differentiation. Though rare, the co-existence of TSC and KC has been reported7-9 and a 4-base-pair deletion in TSC2 was identified.9 In the present investigation, mutation of g.135797247A>G (c.622A>G, p.Ser208Gly) located in exon 7 of TSC1 gene was detected. This mutation caused a conformational change in the wild-type protein and has not been previously reported in patients with or without TSC. The residue has been considered a distinct functional and/or structural sequence of the TSC1 gene. Moreover, the variant was predicted as probably damaging and highly conserved among species. In the family in which the novel mutation was detected, TSC symptoms were not found in any family member.
ClinVar Genomic variation as it relates to human health
NM_000368.5(TSC1):c.622A>G (p.Ser208Gly)
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.
Likely pathogenic
1
no assertion criteria provided
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000368.5(TSC1):c.622A>G (p.Ser208Gly)
Variation ID: 2430291 Accession: VCV002430291.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q34.13 9: 132921860 (GRCh38) [ NCBI UCSC ] 9: 135797247 (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 Mar 5, 2023 Mar 4, 2023 Feb 25, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000368.5:c.622A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000359.1:p.Ser208Gly missense NM_001162426.2:c.622A>G NP_001155898.1:p.Ser208Gly missense NM_001162427.2:c.469A>G NP_001155899.1:p.Ser157Gly missense NM_001362177.2:c.259A>G NP_001349106.1:p.Ser87Gly missense NM_001406592.1:c.622A>G NP_001393521.1:p.Ser208Gly missense NM_001406593.1:c.622A>G NP_001393522.1:p.Ser208Gly missense NM_001406594.1:c.622A>G NP_001393523.1:p.Ser208Gly missense NM_001406595.1:c.622A>G NP_001393524.1:p.Ser208Gly missense NM_001406596.1:c.622A>G NP_001393525.1:p.Ser208Gly missense NM_001406597.1:c.622A>G NP_001393526.1:p.Ser208Gly missense NM_001406598.1:c.622A>G NP_001393527.1:p.Ser208Gly missense NM_001406599.1:c.622A>G NP_001393528.1:p.Ser208Gly missense NM_001406600.1:c.622A>G NP_001393529.1:p.Ser208Gly missense NM_001406601.1:c.622A>G NP_001393530.1:p.Ser208Gly missense NM_001406602.1:c.622A>G NP_001393531.1:p.Ser208Gly missense NM_001406603.1:c.622A>G NP_001393532.1:p.Ser208Gly missense NM_001406604.1:c.622A>G NP_001393533.1:p.Ser208Gly missense NM_001406605.1:c.622A>G NP_001393534.1:p.Ser208Gly missense NM_001406606.1:c.622A>G NP_001393535.1:p.Ser208Gly missense NM_001406607.1:c.622A>G NP_001393536.1:p.Ser208Gly missense NM_001406608.1:c.622A>G NP_001393537.1:p.Ser208Gly missense NM_001406609.1:c.622A>G NP_001393538.1:p.Ser208Gly missense NM_001406610.1:c.469A>G NP_001393539.1:p.Ser157Gly missense NM_001406611.1:c.469A>G NP_001393540.1:p.Ser157Gly missense NM_001406612.1:c.469A>G NP_001393541.1:p.Ser157Gly missense NM_001406613.1:c.469A>G NP_001393542.1:p.Ser157Gly missense NM_001406614.1:c.259A>G NP_001393543.1:p.Ser87Gly missense NM_001406615.1:c.259A>G NP_001393544.1:p.Ser87Gly missense NM_001406616.1:c.259A>G NP_001393545.1:p.Ser87Gly missense NM_001406617.1:c.259A>G NP_001393546.1:p.Ser87Gly missense NM_001406618.1:c.259A>G NP_001393547.1:p.Ser87Gly missense NM_001406619.1:c.259A>G NP_001393548.1:p.Ser87Gly missense NM_001406620.1:c.259A>G NP_001393549.1:p.Ser87Gly missense NM_001406621.1:c.259A>G NP_001393550.1:p.Ser87Gly missense NM_001406622.1:c.259A>G NP_001393551.1:p.Ser87Gly missense NM_001406623.1:c.259A>G NP_001393552.1:p.Ser87Gly missense NM_001406624.1:c.259A>G NP_001393553.1:p.Ser87Gly missense NM_001406625.1:c.259A>G NP_001393554.1:p.Ser87Gly missense NM_001406626.1:c.-256A>G NM_001406627.1:c.-256A>G NM_001406628.1:c.-256A>G NM_001406629.1:c.-398A>G NM_001406630.1:c.-472A>G NR_176214.1:n.839A>G NR_176215.1:n.839A>G NR_176216.1:n.706A>G NR_176217.1:n.839A>G NR_176218.1:n.839A>G NC_000009.12:g.132921860T>C NC_000009.11:g.135797247T>C NG_012386.1:g.27774A>G LRG_486:g.27774A>G LRG_486t1:c.622A>G LRG_486p1:p.Ser208Gly - Protein change
- S157G, S208G, S87G
- Other names
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- Canonical SPDI
- NC_000009.12:132921859:T: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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| TSC1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4848 | 4906 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
no assertion criteria provided
|
Feb 25, 2023 | RCV003128469.2 |
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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Likely pathogenic
(Feb 25, 2023)
|
no assertion criteria provided
Method: case-control
|
Keratoconus
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
inherited
|
Refractive Surgery Department, Bright Eye Hospital
Accession: SCV003804463.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Comment:
TSC is a disorder that causes hamartomas in multiple organs (e.g., brain, eyes, skin, kidneys). The pathogenesis of TSC involves changes in cellular proliferation and … (more)
TSC is a disorder that causes hamartomas in multiple organs (e.g., brain, eyes, skin, kidneys). The pathogenesis of TSC involves changes in cellular proliferation and differentiation. Though rare, the co-existence of TSC and KC has been reported7-9 and a 4-base-pair deletion in TSC2 was identified.9 In the present investigation, mutation of g.135797247A>G (c.622A>G, p.Ser208Gly) located in exon 7 of TSC1 gene was detected. This mutation caused a conformational change in the wild-type protein and has not been previously reported in patients with or without TSC. The residue has been considered a distinct functional and/or structural sequence of the TSC1 gene. Moreover, the variant was predicted as probably damaging and highly conserved among species. In the family in which the novel mutation was detected, TSC symptoms were not found in any family member. (less)
Number of individuals with the variant: 2
Age: 11-46 years
Sex: mixed
Ethnicity/Population group: Han
Geographic origin: China
Comment on evidence:
The proband (II.1) was a 9-year-old boy. He presented with impaired vision, acute keratoconus edema, and rupture of the Descemet’s membrane in the right eye … (more)
The proband (II.1) was a 9-year-old boy. He presented with impaired vision, acute keratoconus edema, and rupture of the Descemet’s membrane in the right eye after rubbing the eye 10 days prior. The uncorrected distance vision acuity (UDVA) was 10/50 (right eye) and 20/50 (left eye). His corrected distance vision acuity (CDVA) was 10/50 (right eye) with -3.00 DS/-6.50 DC × 170° and 20/20 (left eye) with -2.00 DS/-1.00 DC × 165° (Fig. 2). The mean posterior elevation of the cornea (PEC) was 166 µm (right eye) and 25 µm (left eye). Another patient from family 1, subject I.1, was a 46-year-old female. Her UDVAs were 10/50 and CDVAs were 20/20 in both eyes, with -3.25 DS/-1.00 DC × 175° and -4.50 DS/-0.50 DC × 10°. The mean PEC was 15 µm in one eye and 16 µm in another. The central corneal thickness (CCT) was 493 and 491 µm. (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:
TSC is a disorder that causes hamartomas in multiple organs (e.g., brain, eyes, skin, kidneys). The pathogenesis of TSC involves changes in cellular proliferation and differentiation. Though rare, the co-existence of TSC and KC has been reported7-9 and a 4-base-pair deletion in TSC2 was identified.9 In the present investigation, mutation of g.135797247A>G (c.622A>G, p.Ser208Gly) located in exon 7 of TSC1 gene was detected. This mutation caused a conformational change in the wild-type protein and has not been previously reported in patients with or without TSC. The residue has been considered a distinct functional and/or structural sequence of the TSC1 gene. Moreover, the variant was predicted as probably damaging and highly conserved among species. In the family in which the novel mutation was detected, TSC symptoms were not found in any family member.
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 23, 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.