ClinVar Genomic variation as it relates to human health
NM_001182.5(ALDH7A1):c.1046G>C (p.Arg349Thr)
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_001182.5(ALDH7A1):c.1046G>C (p.Arg349Thr)
Variation ID: 204841 Accession: VCV000204841.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q23.2 5: 126555978 (GRCh38) [ NCBI UCSC ] 5: 125891670 (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 May 29, 2016 Aug 18, 2024 Sep 27, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001182.5:c.1046G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001173.2:p.Arg349Thr missense NM_001201377.2:c.962G>C NP_001188306.1:p.Arg321Thr missense NM_001202404.2:c.1008+3262G>C intron variant NC_000005.10:g.126555978C>G NC_000005.9:g.125891670C>G NG_008600.2:g.44413G>C - Protein change
- R349T, R321T
- Other names
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p.R349T:AGA>ACA
- Canonical SPDI
- NC_000005.10:126555977:C:G
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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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The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00004
- 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 | ||
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HI score
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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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ALDH7A1 | - | - |
GRCh38 GRCh37 |
1074 | 1117 |
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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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Dec 8, 2014 | RCV000186738.3 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Sep 27, 2023 | RCV000690729.12 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 23, 2019 | RCV002399694.2 |
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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Uncertain significance
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Pyridoxine-dependent epilepsy
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000897183.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Uncertain significance
(Dec 08, 2014)
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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: SCV000240305.11
First in ClinVar: Aug 07, 2015 Last updated: May 29, 2016 |
Comment:
p.Arg349Thr (AGA>ACA): c.1046 G>C in exon 12 of the ALDH7A1 gene (NM_001182.4). The R349T variant has not been published as a mutation, nor has it … (more)
p.Arg349Thr (AGA>ACA): c.1046 G>C in exon 12 of the ALDH7A1 gene (NM_001182.4). The R349T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is not conserved across species. However, the R349T variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In addition, a missense mutation in a nearby residue (Y354C) has been reported in association with pyridoxine-dependent epilepsy. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). (less)
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Uncertain significance
(Aug 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Pyridoxine-dependent epilepsy
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000818429.5
First in ClinVar: Oct 10, 2018 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 349 of the ALDH7A1 protein (p.Arg349Thr). … (more)
This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 349 of the ALDH7A1 protein (p.Arg349Thr). This variant is present in population databases (rs553114356, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ALDH7A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 204841). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ALDH7A1 protein function. 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. (less)
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Uncertain significance
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pyridoxine-dependent epilepsy
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004048924.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
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Uncertain significance
(Sep 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pyridoxine-dependent epilepsy
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003823150.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Sep 23, 2019)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002710032.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.R349T variant (also known as c.1046G>C), located in coding exon 12 of the ALDH7A1 gene, results from a G to C substitution at nucleotide … (more)
The p.R349T variant (also known as c.1046G>C), located in coding exon 12 of the ALDH7A1 gene, results from a G to C substitution at nucleotide position 1046. The arginine at codon 349 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005188568.1
First in ClinVar: Aug 18, 2024 Last updated: Aug 18, 2024 |
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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
HelpThere 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 rs553114356 ...
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.