ClinVar Genomic variation as it relates to human health
NM_000255.4(MMUT):c.2200C>T (p.Gln734Ter)
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_000255.4(MMUT):c.2200C>T (p.Gln734Ter)
Variation ID: 222943 Accession: VCV000222943.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6p12.3 6: 49431781 (GRCh38) [ NCBI UCSC ] 6: 49399494 (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 Jul 25, 2016 Apr 6, 2024 Feb 11, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000255.4:c.2200C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000246.2:p.Gln734Ter nonsense NC_000006.12:g.49431781G>A NC_000006.11:g.49399494G>A NG_007100.1:g.36359C>T - Protein change
- Q734*
- Other names
- -
- Canonical SPDI
- NC_000006.12:49431780: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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
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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MMUT | - | - |
GRCh38 GRCh37 |
1077 | 1090 |
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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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Feb 11, 2024 | RCV000236154.11 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 8, 2022 | RCV000284154.7 |
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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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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University Children's Hospital, University of Zurich
Accession: SCV000262815.1
First in ClinVar: Jul 25, 2016 Last updated: Jul 25, 2016 |
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Pathogenic
(Sep 08, 2016)
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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: SCV000329615.6
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
The Q734X variant has been reported previously in patients with methylmalonic acidemia (Mohamed et al. 2015; Imtiaz et al. 2015; Forny et al. 2016). Q734X … (more)
The Q734X variant has been reported previously in patients with methylmalonic acidemia (Mohamed et al. 2015; Imtiaz et al. 2015; Forny et al. 2016). Q734X was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q734X variant is predicted to cause loss of normal protein function through protein truncation. In summary, we interpret Q734X to be a pathogenic variant. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
Affected status: yes
Allele origin:
germline
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Pathology and Clinical Laboratory Medicine, King Fahad Medical City
Accession: SCV001438919.1
First in ClinVar: Oct 25, 2020 Last updated: Oct 25, 2020 |
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
Geographic origin: Middle East
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Pathogenic
(Sep 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002017620.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Mar 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003439389.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 222943). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 222943). This premature translational stop signal has been observed in individual(s) with methylmalonic aciduria (PMID: 26318470, 26615597, 27167370). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln734*) in the MUT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 17 amino acid(s) of the MUT protein. (less)
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Pathogenic
(Feb 11, 2024)
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criteria provided, single submitter
Method: research
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Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004800990.2
First in ClinVar: Mar 16, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Apr 01, 2023)
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no assertion criteria provided
Method: clinical testing
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Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
Affected status: yes
Allele origin:
germline
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Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)
Accession: SCV003927915.1
First in ClinVar: Sep 16, 2023 Last updated: Sep 16, 2023 |
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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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Molecular Genetic Characterization of 151 Mut-Type Methylmalonic Aciduria Patients and Identification of 41 Novel Mutations in MUT. | Forny P | Human mutation | 2016 | PMID: 27167370 |
Spectrum of Mutations in 60 Saudi Patients with Mut Methylmalonic Acidemia. | Imtiaz F | JIMD reports | 2016 | PMID: 26615597 |
Identification of 2 novel homozygous mutations in the methylmalonyl-CoA mutase gene in Saudi patients. | Mohamed S | Saudi medical journal | 2015 | PMID: 26318470 |
Text-mined citations for rs879253852 ...
HelpRecord 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.