ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.5017G>C (p.Val1673Leu)
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.5017G>C (p.Val1673Leu)
Variation ID: 49495 Accession: VCV000049495.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2087890 (GRCh38) [ NCBI UCSC ] 16: 2137891 (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 16, 2013 Mar 16, 2024 Jan 30, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.5017G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Val1673Leu missense NM_000548.4:c.5017G>C NM_001077183.3:c.4816G>C NP_001070651.1:p.Val1606Leu missense NM_001114382.3:c.4948G>C NP_001107854.1:p.Val1650Leu missense NM_001318827.2:c.4708G>C NP_001305756.1:p.Val1570Leu missense NM_001318829.2:c.4672G>C NP_001305758.1:p.Val1558Leu missense NM_001318831.2:c.4285G>C NP_001305760.1:p.Val1429Leu missense NM_001318832.2:c.4849G>C NP_001305761.1:p.Val1617Leu missense NM_001363528.2:c.4819G>C NP_001350457.1:p.Val1607Leu missense NM_001370404.1:c.4885G>C NP_001357333.1:p.Val1629Leu missense NM_001370405.1:c.4888G>C NP_001357334.1:p.Val1630Leu missense NM_021055.3:c.4888G>C NP_066399.2:p.Val1630Leu missense NC_000016.10:g.2087890G>C NC_000016.9:g.2137891G>C NG_005895.1:g.43585G>C NG_008617.1:g.55331C>G LRG_487:g.43585G>C LRG_487t1:c.5017G>C P49815:p.Val1673Leu - Protein change
- V1673L, V1429L, V1617L, V1558L, V1570L, V1607L, V1629L, V1650L, V1606L, V1630L
- Other names
- p.V1673L:GTC>CTC
- Canonical SPDI
- NC_000016.10:2087889: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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0.00060 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00003
1000 Genomes Project 30x 0.00047
1000 Genomes Project 0.00060
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
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 |
10489 | 10664 |
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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not provided (1) |
no classification provided
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- | RCV000042755.3 | |
not provided (1) |
no classification provided
|
Sep 19, 2013 | RCV000122240.5 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 30, 2024 | RCV000535012.10 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jul 13, 2021 | RCV000568994.3 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 11, 2022 | RCV001703934.2 | |
Benign (1) |
criteria provided, single submitter
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Sep 15, 2020 | RCV003974928.1 |
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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Benign
(Feb 15, 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: SCV000243712.11
First in ClinVar: Aug 07, 2015 Last updated: Apr 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 24728327, 15595939, 28991257)
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Likely benign
(Jul 13, 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: SCV002534004.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Sep 15, 2020)
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criteria provided, single submitter
Method: clinical testing
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TSC2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004792980.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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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: SCV002039888.1
First in ClinVar: Dec 25, 2021 Last updated: Dec 25, 2021 |
|
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Benign
(Jul 08, 2016)
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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: SCV000675497.4
First in ClinVar: Jan 01, 2018 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: 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)
Number of individuals with the variant: 1
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Benign
(Feb 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004221464.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
|
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Benign
(Jan 30, 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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Invitae
Accession: SCV000644594.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
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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: SCV000086463.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
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: SCV000066550.3
First in ClinVar: May 04, 2013 Last updated: Sep 16, 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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Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. | Jin SC | Nature genetics | 2017 | PMID: 28991257 |
Mutation and polymorphism analysis of TSC1 and TSC2 genes in Indian patients with tuberous sclerosis complex. | Ali M | Acta neurologica Scandinavica | 2005 | PMID: 15595939 |
Text-mined citations for rs45490993 ...
HelpRecord last updated Mar 17, 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.