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. This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.43_48dup, results in the insertion of 2 amino acid(s) of the RET protein (p.Leu18_Leu19dup), but otherwise preserves the integrity of the reading frame.
ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.43_48dup (p.Leu19_Pro20insLeuLeu)
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)
Help
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_020975.6(RET):c.43_48dup (p.Leu19_Pro20insLeuLeu)
Variation ID: 3022887 Accession: VCV003022887.1
- Type and length
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Duplication, 6 bp
- Location
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Cytogenetic: 10q11.21 10: 43077295-43077296 (GRCh38) [ NCBI UCSC ] 10: 43572743-43572744 (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 Feb 29, 2024 Feb 28, 2024 Dec 9, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_020975.6:c.43_48dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_000323.2:c.43_48dup NP_000314.1:p.Leu19_Pro20insLeuLeu inframe indel NM_001406743.1:c.43_48dup NP_001393672.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406744.1:c.43_48dup NP_001393673.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406759.1:c.43_48dup NP_001393688.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406760.1:c.43_48dup NP_001393689.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406761.1:c.43_48dup NP_001393690.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406762.1:c.43_48dup NP_001393691.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406763.1:c.43_48dup NP_001393692.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406764.1:c.43_48dup NP_001393693.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406765.1:c.43_48dup NP_001393694.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406766.1:c.43_48dup NP_001393695.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406767.1:c.43_48dup NP_001393696.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406768.1:c.43_48dup NP_001393697.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406769.1:c.43_48dup NP_001393698.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406770.1:c.43_48dup NP_001393699.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406771.1:c.43_48dup NP_001393700.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406772.1:c.43_48dup NP_001393701.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406773.1:c.43_48dup NP_001393702.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406774.1:c.43_48dup NP_001393703.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406775.1:c.43_48dup NP_001393704.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406776.1:c.43_48dup NP_001393705.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406777.1:c.43_48dup NP_001393706.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406778.1:c.43_48dup NP_001393707.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406779.1:c.43_48dup NP_001393708.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406780.1:c.43_48dup NP_001393709.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406781.1:c.43_48dup NP_001393710.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406782.1:c.43_48dup NP_001393711.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406783.1:c.43_48dup NP_001393712.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406784.1:c.43_48dup NP_001393713.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406785.1:c.43_48dup NP_001393714.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406786.1:c.43_48dup NP_001393715.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406787.1:c.43_48dup NP_001393716.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406788.1:c.43_48dup NP_001393717.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406789.1:c.43_48dup NP_001393718.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406790.1:c.43_48dup NP_001393719.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406791.1:c.43_48dup NP_001393720.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406792.1:c.43_48dup NP_001393721.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406793.1:c.43_48dup NP_001393722.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_001406794.1:c.43_48dup NP_001393723.1:p.Leu19_Pro20insLeuLeu inframe insertion NM_020629.2:c.43_48dup NP_065680.1:p.Leu19_Pro20insLeuLeu inframe indel NM_020630.7:c.43_48dup NP_065681.1:p.Leu19_Pro20insLeuLeu inframe insertion NC_000010.11:g.43077301_43077306dup NC_000010.10:g.43572749_43572754dup NG_007489.1:g.5233_5238dup NG_045003.1:g.4488_4493dup LRG_518:g.5233_5238dup LRG_518t1:c.43_48dup LRG_518p1:p.Leu19_Pro20insLeuLeu LRG_518t2:c.43_48dup LRG_518p2:p.Leu19_Pro20insLeuLeu - Protein change
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- Other names
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- Canonical SPDI
- NC_000010.11:43077295:TGCTGTTGCTG:TGCTGTTGCTGTTGCTG
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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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| RET | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3598 | 3720 | |
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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Dec 9, 2022 | RCV003882073.2 |
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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Uncertain significance
(Dec 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Multiple endocrine neoplasia, type 2
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004687499.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Comment:
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 … (more)
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. This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.43_48dup, results in the insertion of 2 amino acid(s) of the RET protein (p.Leu18_Leu19dup), but otherwise preserves the integrity of the reading frame. (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:
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. This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.43_48dup, results in the insertion of 2 amino acid(s) of the RET protein (p.Leu18_Leu19dup), but otherwise preserves the integrity of the reading frame.
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 Sep 30, 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.