ClinVar Genomic variation as it relates to human health
NM_015141.4(GPD1L):c.370A>G (p.Ile124Val)
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.
Uncertain significance(2); Benign(3); Likely benign(7)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_015141.4(GPD1L):c.370A>G (p.Ile124Val)
Variation ID: 788 Accession: VCV000000788.50
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p22.3 3: 32140231 (GRCh38) [ NCBI UCSC ] 3: 32181723 (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 Apr 4, 2013 May 1, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_015141.4:c.370A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055956.1:p.Ile124Val missense NC_000003.12:g.32140231A>G NC_000003.11:g.32181723A>G NG_023375.1:g.38721A>G LRG_419:g.38721A>G LRG_419t1:c.370A>G LRG_419p1:p.Ile124Val Q8N335:p.Ile124Val - Protein change
- I124V
- Other names
- p.I124V:ATA>GTA
- Canonical SPDI
- NC_000003.12:32140230:A: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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0.00080 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00078
1000 Genomes Project 0.00080
Trans-Omics for Precision Medicine (TOPMed) 0.00091
Exome Aggregation Consortium (ExAC) 0.00205
The Genome Aggregation Database (gnomAD), exomes 0.00251
The Genome Aggregation Database (gnomAD) 0.00291
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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GPD1L | - | - |
GRCh38 GRCh37 |
360 | 396 |
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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Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Oct 26, 2023 | RCV000000824.15 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 24, 2013 | RCV000029945.4 | |
Likely benign (1) |
no assertion criteria provided
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Nov 4, 2014 | RCV000157243.2 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jul 25, 2018 | RCV000170920.11 | |
Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
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Jul 23, 2019 | RCV000203752.28 | |
Likely benign (1) |
criteria provided, single submitter
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Oct 9, 2018 | RCV000620285.4 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 12, 2018 | RCV000852958.2 | |
Benign (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV001081825.5 | |
Likely benign (1) |
criteria provided, single submitter
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Dec 11, 2023 | RCV003952333.1 |
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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Likely benign
(Jun 24, 2013)
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criteria provided, single submitter
Method: research
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Sudden infant death syndrome
Affected status: unknown
Allele origin:
unknown
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000050768.1 First in ClinVar: Jun 04, 2015 Last updated: Jun 04, 2015
Comments (2):
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less)
Medical sequencing
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Number of individuals with the variant: 3
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Benign
(Mar 29, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000539250.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 1.2% (82/6614) Finnish chromosomes (less)
Method: Genome/Exome Filtration
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Brugada syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000262445.9
First in ClinVar: Jan 31, 2016 Last updated: Feb 28, 2024 |
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Likely benign
(Dec 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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GPD1L-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004774886.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Uncertain significance
(Dec 01, 2018)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001153827.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 2
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Likely benign
(Nov 21, 2018)
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criteria provided, single submitter
Method: clinical testing
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Brugada syndrome 2
Affected status: unknown
Allele origin:
unknown
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000883145.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
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Likely benign
(Mar 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
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Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego
Accession: SCV000995707.1
First in ClinVar: Oct 12, 2019 Last updated: Oct 12, 2019 |
Number of individuals with the variant: 1
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Uncertain significance
(Oct 19, 2020)
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criteria provided, single submitter
Method: clinical testing
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Brugada syndrome 2
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001934251.1
First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
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Likely benign
(Jul 25, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052600.4
First in ClinVar: Apr 04, 2013 Last updated: Dec 11, 2022 |
Comment:
Variant summary: GPD1L c.370A>G (p.Ile124Val) results in a conservative amino acid change located in the N-terminal of the Glycerol-3-phosphate dehydrogenase, NAD-dependent domain (IPR011128) of the … (more)
Variant summary: GPD1L c.370A>G (p.Ile124Val) results in a conservative amino acid change located in the N-terminal of the Glycerol-3-phosphate dehydrogenase, NAD-dependent domain (IPR011128) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0029 in 277792 control chromosomes in the gnomAD database and publications, including 7 homozygotes. The observed variant frequency is approximately 289-fold of the estimated maximal expected allele frequency for a pathogenic variant in GPD1L causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. The variant, c.370A>G, has been reported in the literature in individuals affected with SIDS, sudden death, and atrial fibrillation (VanNorstrand_2007, Skinner_2014, Husser_2017). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (VanNorstrand_2007). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign. (less)
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Likely benign
(Jul 23, 2019)
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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: SCV000223478.16
First in ClinVar: May 23, 2015 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 22995991, 19606473, 29077258, 17967976, 24055113, 23465283, 21215473, 25395996, 25998140, 23295036, 24715918, 28837624, 30615648, 15140536, 31019283, 31043699, … (more)
This variant is associated with the following publications: (PMID: 22995991, 19606473, 29077258, 17967976, 24055113, 23465283, 21215473, 25395996, 25998140, 23295036, 24715918, 28837624, 30615648, 15140536, 31019283, 31043699, 30847666) (less)
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Benign
(Oct 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Brugada syndrome 2
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157163.2
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Likely benign
(Oct 09, 2018)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000737734.5
First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Pathogenic
(Nov 13, 2007)
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no assertion criteria provided
Method: literature only
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BRUGADA SYNDROME 2
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000020974.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In a 5-week-old white girl who died of SIDS (272120; see also Brugada syndrome-2, 611777), Van Norstrand et al. (2007) identified a 430A-G transition in … (more)
In a 5-week-old white girl who died of SIDS (272120; see also Brugada syndrome-2, 611777), Van Norstrand et al. (2007) identified a 430A-G transition in the GPD1L gene, resulting in an ile124-to-val (I124V) substitution at a highly conserved residue in the N-terminal NAD binding domain. The I124V mutation, which significantly reduced the sodium current in HEK cells and neonatal mouse cardiomyocytes, was not found in 600 reference alleles. (less)
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Likely benign
(Nov 04, 2014)
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no assertion criteria provided
Method: clinical testing
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Primary familial hypertrophic cardiomyopathy
Long QT syndrome
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV000206970.1
First in ClinVar: Feb 06, 2015 Last updated: Feb 06, 2015 |
Number of individuals with the variant: 1
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001922519.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001930037.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954138.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001968706.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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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Rare variants in genes encoding the cardiac sodium channel and associated compounds and their impact on outcome of catheter ablation of atrial fibrillation. | Husser D | PloS one | 2017 | PMID: 28837624 |
High prevalence of concealed Brugada syndrome in patients with atrioventricular nodal reentrant tachycardia. | Hasdemir C | Heart rhythm | 2015 | PMID: 25998140 |
Diabetic Dead-in-Bed Syndrome: A Possible Link to a Cardiac Ion Channelopathy. | Skinner JR | Case reports in medicine | 2014 | PMID: 24715918 |
Actionable, pathogenic incidental findings in 1,000 participants' exomes. | Dorschner MO | American journal of human genetics | 2013 | PMID: 24055113 |
Mutations in genes encoding cardiac ion channels previously associated with sudden infant death syndrome (SIDS) are present with high frequency in new exome data. | Andreasen C | The Canadian journal of cardiology | 2013 | PMID: 23465283 |
An informatics approach to analyzing the incidentalome. | Berg JS | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22995991 |
Cardiac metabolic state and Brugada syndrome: a link revealed. | Chahine M | Circulation research | 2009 | PMID: 19815826 |
The genetic basis of Brugada syndrome: a mutation update. | Hedley PL | Human mutation | 2009 | PMID: 19606473 |
Molecular and functional characterization of novel glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) mutations in sudden infant death syndrome. | Van Norstrand DW | Circulation | 2007 | PMID: 17967976 |
Prevalence and prognosis of subjects with Brugada-type ECG pattern in a young and middle-aged Finnish population. | Junttila MJ | European heart journal | 2004 | PMID: 15140536 |
Text-mined citations for rs72552293 ...
HelpRecord last updated May 01, 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.