Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Clark-Baraitser syndrome MIM#617752. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (v2: 1 heterozygote, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Pro193Arg) has been reported de novo in an individual with abnormality of the nervous system (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. It has been reported de novo in an affected individual and classified as likely pathogenic by a diagnostic laboratory in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
ClinVar Genomic variation as it relates to human health
NM_001348323.3(TRIP12):c.5801C>T (p.Pro1934Leu)
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.
(4)
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.
Conflicting classifications of pathogenicity
Pathogenic(1); Likely pathogenic(1); Uncertain significance(1)
Pathogenic(1); Likely pathogenic(1); Uncertain significance(1)
4
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001348323.3(TRIP12):c.5801C>T (p.Pro1934Leu)
Variation ID: 620003 Accession: VCV000620003.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q36.3 2: 229771526 (GRCh38) [ NCBI UCSC ] 2: 230636242 (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 19, 2019 Jul 23, 2024 Jun 24, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001348323.3:c.5801C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001335252.1:p.Pro1934Leu missense NM_001284214.2:c.5720C>T NP_001271143.1:p.Pro1907Leu missense NM_001284215.2:c.5675C>T NP_001271144.1:p.Pro1892Leu missense NM_001284216.2:c.4766C>T NP_001271145.1:p.Pro1589Leu missense NM_001348315.2:c.5720C>T NP_001335244.1:p.Pro1907Leu missense NM_001348316.2:c.5675C>T NP_001335245.1:p.Pro1892Leu missense NM_001348317.1:c.5660C>T NP_001335246.1:p.Pro1887Leu missense NM_001348318.2:c.5660C>T NP_001335247.1:p.Pro1887Leu missense NM_001348319.1:c.5786C>T NP_001335248.1:p.Pro1929Leu missense NM_001348320.2:c.5786C>T NP_001335249.1:p.Pro1929Leu missense NM_001348321.1:c.5789C>T NP_001335250.1:p.Pro1930Leu missense NM_001348322.1:c.5801C>T NP_001335251.1:p.Pro1934Leu missense NM_001348324.2:c.5801C>T NP_001335253.1:p.Pro1934Leu missense NM_001348325.2:c.5801C>T NP_001335254.1:p.Pro1934Leu missense NM_001348326.2:c.5801C>T NP_001335255.1:p.Pro1934Leu missense NM_001348327.2:c.5801C>T NP_001335256.1:p.Pro1934Leu missense NM_001348328.1:c.5804C>T NP_001335257.1:p.Pro1935Leu missense NM_001348329.2:c.5804C>T NP_001335258.1:p.Pro1935Leu missense NM_001348330.2:c.5804C>T NP_001335259.1:p.Pro1935Leu missense NM_001348331.1:c.5579C>T NP_001335260.1:p.Pro1860Leu missense NM_001348332.1:c.5699C>T NP_001335261.1:p.Pro1900Leu missense NM_001348333.1:c.5723C>T NP_001335262.1:p.Pro1908Leu missense NM_004238.1:c.5576C>T NM_004238.3:c.5576C>T NP_004229.1:p.Pro1859Leu missense NC_000002.12:g.229771526G>A NC_000002.11:g.230636242G>A NG_053017.1:g.156709C>T - Protein change
- P1892L, P1907L, P1935L, P1860L, P1900L, P1908L, P1930L, P1589L, P1859L, P1887L, P1929L, P1934L
- Other names
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- Canonical SPDI
- NC_000002.12:229771525:G:A
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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. |
|||
| TRIP12 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
427 | 481 | |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Jun 24, 2022 | RCV000760205.10 |
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
(Jul 17, 2019)
|
criteria provided, single submitter
Method: clinical testing
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Clark-Baraitser syndrome
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003821512.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely pathogenic
(Aug 30, 2017)
|
criteria provided, single submitter
Method: clinical testing
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Clark-Baraitser syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Génétique des Maladies du Développement, Hospices Civils de Lyon
Accession: SCV000890035.1
First in ClinVar: Mar 19, 2019 Last updated: Mar 19, 2019 |
|
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Pathogenic
(Jun 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Clark-Baraitser syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002557818.2
First in ClinVar: Aug 08, 2022 Last updated: Jul 23, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Clark-Baraitser syndrome MIM#617752. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (v2: 1 heterozygote, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Pro193Arg) has been reported de novo in an individual with abnormality of the nervous system (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. It has been reported de novo in an affected individual and classified as likely pathogenic by a diagnostic laboratory in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Clark-Baraitser syndrome
Affected status: yes
Allele origin:
unknown
|
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea
Accession: SCV004697955.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
|
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:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Clark-Baraitser syndrome MIM#617752. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (v2: 1 heterozygote, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Pro193Arg) has been reported de novo in an individual with abnormality of the nervous system (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. It has been reported de novo in an affected individual and classified as likely pathogenic by a diagnostic laboratory in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
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 Jul 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.