Variant summary: TULP1 c.901C>T (p.Gln301X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 249232 control chromosomes (gnomAD). c.901C>T has been reported in the compound heterozygous and homozygous state in numerous patients affected with Leber congenital amaurosis, Retinitis pigmentosa or Cone dystrophy (Li_2009, Abu-Safieh_2013, Khan_2015). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
ClinVar Genomic variation as it relates to human health
NM_003322.6(TULP1):c.901C>T (p.Gln301Ter)
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.
(8)
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.
Pathogenic
8
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_003322.6(TULP1):c.901C>T (p.Gln301Ter)
Variation ID: 828151 Accession: VCV000828151.36
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 6p21.31 6: 35506101 (GRCh38) [ NCBI UCSC ] 6: 35473878 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 29, 2020 Apr 6, 2024 Mar 17, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_003322.6:c.901C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003313.3:p.Gln301Ter nonsense NM_001289395.2:c.742C>T NP_001276324.1:p.Gln248Ter nonsense NC_000006.12:g.35506101G>A NC_000006.11:g.35473878G>A NG_009077.1:g.11770C>T - Protein change
- Q248*, Q301*
- Other names
- -
- Canonical SPDI
- NC_000006.12:35506100:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00020 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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. |
|||
| TULP1 | - | - |
GRCh38 GRCh37 |
785 | 795 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
no assertion criteria provided
|
Feb 5, 2020 | RCV001028029.1 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 10, 2021 | RCV001814258.1 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 2, 2020 | RCV001251337.1 | |
| Pathogenic (1) |
no assertion criteria provided
|
Sep 10, 2015 | RCV001257786.1 | |
| Pathogenic (2) |
criteria provided, single submitter
|
Mar 17, 2024 | RCV001255925.4 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Dec 5, 2023 | RCV001054314.12 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Mar 17, 2024)
|
criteria provided, single submitter
Method: research
|
Leber congenital amaurosis 15
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004804683.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
|
|
|
Pathogenic
(Jul 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Leber congenital amaurosis
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001426900.1
First in ClinVar: Aug 09, 2020 Last updated: Aug 09, 2020 |
Comment:
Variant summary: TULP1 c.901C>T (p.Gln301X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: TULP1 c.901C>T (p.Gln301X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 249232 control chromosomes (gnomAD). c.901C>T has been reported in the compound heterozygous and homozygous state in numerous patients affected with Leber congenital amaurosis, Retinitis pigmentosa or Cone dystrophy (Li_2009, Abu-Safieh_2013, Khan_2015). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Feb 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001480106.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
Clinical Features:
Rod-cone dystrophy (present) , Cone-rod dystrophy (present)
Sex: female
|
|
|
Pathogenic
(Jul 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Abnormality of the eye
Affected status: yes
Allele origin:
germline
|
Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV001755327.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
|
|
|
Pathogenic
(Dec 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001218623.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln301*) in the TULP1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln301*) in the TULP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TULP1 are known to be pathogenic (PMID: 8606774, 10549638, 15024725, 18055821). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal recessive inherited retinal dystrophy (PMID: 18936139, 25342276). ClinVar contains an entry for this variant (Variation ID: 828151). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Feb 05, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Retinitis pigmentosa 14
Affected status: yes
Allele origin:
germline
|
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001190794.1
First in ClinVar: Mar 29, 2020 Last updated: Mar 29, 2020 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Leber congenital amaurosis 15
Affected status: yes
Allele origin:
inherited
|
Laboratory of Genetics in Ophthalmology, Institut Imagine
Accession: SCV001432533.1
First in ClinVar: Sep 19, 2020 Last updated: Sep 19, 2020 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Sep 10, 2015)
|
no assertion criteria provided
Method: literature only
|
Autosomal recessive Retinitis Pigmentosa
Affected status: yes
Allele origin:
germline
|
Faculty of Health Sciences, Beirut Arab University
Accession: SCV001434649.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Observation 1:
Number of individuals with the variant: 8
Ethnicity/Population group: Arab
Observation 2:
Number of individuals with the variant: 2
Ethnicity/Population group: Arab
Observation 3:
Number of individuals with the variant: 3
Ethnicity/Population group: Arab
Observation 4:
Number of individuals with the variant: 2
Ethnicity/Population group: Arab
Observation 5:
Number of individuals with the variant: 3
Ethnicity/Population group: Arab
Observation 6:
Number of individuals with the variant: 2
Ethnicity/Population group: Arab
Observation 7:
Number of individuals with the variant: 3
Ethnicity/Population group: Arab
Observation 8:
Number of individuals with the variant: 3
Ethnicity/Population group: Arab
Observation 9:
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
Observation 10:
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
Observation 11:
Number of individuals with the variant: 10
Ethnicity/Population group: Arab
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
Observation 13:
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
Observation 14:
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
Observation 15:
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
Observation 16:
Number of individuals with the variant: 3
Ethnicity/Population group: Arab
Observation 17:
Number of individuals with the variant: 13
Ethnicity/Population group: Arab
Observation 18:
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
Observation 19:
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Gln301*) in the TULP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TULP1 are known to be pathogenic (PMID: 8606774, 10549638, 15024725, 18055821). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal recessive inherited retinal dystrophy (PMID: 18936139, 25342276). ClinVar contains an entry for this variant (Variation ID: 828151). For these reasons, this variant has been classified as Pathogenic.
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:
Variant summary: TULP1 c.901C>T (p.Gln301X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 249232 control chromosomes (gnomAD). c.901C>T has been reported in the compound heterozygous and homozygous state in numerous patients affected with Leber congenital amaurosis, Retinitis pigmentosa or Cone dystrophy (Li_2009, Abu-Safieh_2013, Khan_2015). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Gln301*) in the TULP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TULP1 are known to be pathogenic (PMID: 8606774, 10549638, 15024725, 18055821). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal recessive inherited retinal dystrophy (PMID: 18936139, 25342276). ClinVar contains an entry for this variant (Variation ID: 828151). For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mutations in known disease genes account for the majority of autosomal recessive retinal dystrophies. | Patel N | Clinical genetics | 2018 | PMID: 30054919 |
| Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies. | Patel N | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26355662 |
| A TULP1 founder mutation, p.Gln301*, underlies a recognisable congenital rod-cone dystrophy phenotype on the Arabian Peninsula. | Khan AO | The British journal of ophthalmology | 2015 | PMID: 25342276 |
| Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. | Abu-Safieh L | Genome research | 2013 | PMID: 23105016 |
| Mutation survey of known LCA genes and loci in the Saudi Arabian population. | Li Y | Investigative ophthalmology & visual science | 2009 | PMID: 18936139 |
| Identification of novel mutations in patients with Leber congenital amaurosis and juvenile RP by genome-wide homozygosity mapping with SNP microarrays. | den Hollander AI | Investigative ophthalmology & visual science | 2007 | PMID: 18055821 |
| Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. | Hanein S | Human mutation | 2004 | PMID: 15024725 |
| Retinal degeneration in tulp1-/- mice: vesicular accumulation in the interphotoreceptor matrix. | Hagstrom SA | Investigative ophthalmology & visual science | 1999 | PMID: 10549638 |
| A candidate gene for the mouse mutation tubby. | Noben-Trauth K | Nature | 1996 | PMID: 8606774 |
Text-mined citations for rs201070350 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 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.