ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.1973A>C (p.Lys658Thr)
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.
Uncertain significance(1); Benign(2); Likely benign(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000548.5(TSC2):c.1973A>C (p.Lys658Thr)
Variation ID: 65307 Accession: VCV000065307.31
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2071810 (GRCh38) [ NCBI UCSC ] 16: 2121811 (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 Sep 17, 2013 Oct 8, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.1973A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Lys658Thr missense NM_001077183.3:c.1973A>C NP_001070651.1:p.Lys658Thr missense NM_001114382.3:c.1973A>C NP_001107854.1:p.Lys658Thr missense NM_001318827.2:c.1862A>C NP_001305756.1:p.Lys621Thr missense NM_001318829.2:c.1826A>C NP_001305758.1:p.Lys609Thr missense NM_001318831.2:c.1373A>C NP_001305760.1:p.Lys458Thr missense NM_001318832.2:c.2006A>C NP_001305761.1:p.Lys669Thr missense NM_001363528.2:c.1973A>C NP_001350457.1:p.Lys658Thr missense NM_001370404.1:c.1973A>C NP_001357333.1:p.Lys658Thr missense NM_001370405.1:c.1973A>C NP_001357334.1:p.Lys658Thr missense NM_021055.3:c.1973A>C NP_066399.2:p.Lys658Thr missense NC_000016.10:g.2071810A>C NC_000016.9:g.2121811A>C NG_005895.1:g.27505A>C LRG_487:g.27505A>C LRG_487t1:c.1973A>C - Protein change
- K658T, K458T, K609T, K669T, K621T
- Other names
- p.K658T:AAG>ACG
- Canonical SPDI
- NC_000016.10:2071809:A: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00008
1000 Genomes Project 30x 0.00016
The Genome Aggregation Database (gnomAD) 0.00022
Exome Aggregation Consortium (ExAC) 0.00026
The Genome Aggregation Database (gnomAD), exomes 0.00028
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 | ||
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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
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 |
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
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. |
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Uncertain significance (2) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000055529.13 | |
not provided (1) |
no classification provided
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Sep 19, 2013 | RCV000122212.12 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000234257.20 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Apr 22, 2021 | RCV000564486.12 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Apr 1, 2023 | RCV001703965.18 |
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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Likely benign
(Apr 22, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002531023.1
First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020 |
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Likely benign
(Mar 29, 2019)
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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: SCV000675536.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Likely benign
(May 20, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000243664.13
First in ClinVar: Aug 07, 2015 Last updated: May 29, 2016 |
Comment:
This variant is associated with the following publications: (PMID: 24728327, 22903760, 23514105, 21309039)
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Likely benign
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002039600.1
First in ClinVar: Dec 25, 2021 Last updated: Dec 25, 2021 |
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Likely benign
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011349.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Benign
(Feb 01, 2024)
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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: SCV000285264.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024 |
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Uncertain significance
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Tuberous Sclerosis
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000395597.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Benign
(Apr 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004010421.11
First in ClinVar: Jul 16, 2023 Last updated: Oct 08, 2024 |
Comment:
TSC2: BS3:Supporting, BS1, BS2
Number of individuals with the variant: 1
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000086433.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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not provided
(-)
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no classification provided
Method: curation
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TSC
Affected status: yes
Allele origin:
germline
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Tuberous sclerosis database (TSC2)
Accession: SCV000083752.2
First in ClinVar: Sep 17, 2013 Last updated: Sep 17, 2013 |
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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
HelpTitle | Author | Journal | Year | Link |
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- | - | - | - | PMID: 22903760 |
Text-mined citations for rs397515223 ...
HelpRecord last updated Oct 13, 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.