ClinVar Genomic variation as it relates to human health
NM_001349206.2(LPIN1):c.1029del (p.Gln344fs)
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_001349206.2(LPIN1):c.1029del (p.Gln344fs)
Variation ID: 2444342 Accession: VCV002444342.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2p25.1 2: 11782270 (GRCh38) [ NCBI UCSC ] 2: 11922396 (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 18, 2023 Feb 14, 2024 Jul 22, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001349206.2:c.1029del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001336135.1:p.Gln344fs frameshift NM_001261427.3:c.939del NP_001248356.1:p.Gln314fs frameshift NM_001261428.3:c.1176del NP_001248357.1:p.Gln393fs frameshift NM_001349199.2:c.921del NP_001336128.1:p.Gln308fs frameshift NM_001349200.2:c.921del NP_001336129.1:p.Gln308fs frameshift NM_001349201.2:c.921del NP_001336130.1:p.Gln308fs frameshift NM_001349202.2:c.1026del NP_001336131.1:p.Gln343fs frameshift NM_001349203.2:c.1026del NP_001336132.1:p.Gln343fs frameshift NM_001349204.2:c.1029del NP_001336133.1:p.Gln344fs frameshift NM_001349205.2:c.1029del NP_001336134.1:p.Gln344fs frameshift NM_001349207.2:c.1119del NP_001336136.1:p.Gln374fs frameshift NM_001349208.2:c.1068del NP_001336137.1:p.Gln357fs frameshift NM_145693.4:c.921del NP_663731.1:p.Gln308fs frameshift NR_146080.2:n.970del non-coding transcript variant NC_000002.12:g.11782272del NC_000002.11:g.11922398del NG_012843.2:g.109694del - Protein change
- Q308fs, Q314fs, Q343fs, Q344fs, Q357fs, Q374fs, Q393fs
- Other names
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- Canonical SPDI
- NC_000002.12:11782269:TTT:TT
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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
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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
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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LPIN1 | - | - |
GRCh38 GRCh37 |
597 | 700 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (1) |
criteria provided, single submitter
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Feb 23, 2023 | RCV003153140.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 22, 2023 | RCV003575046.1 |
Submissions - Germline
Classification
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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
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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
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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
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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
(Feb 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Myoglobinuria, acute recurrent, autosomal recessive
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV003841953.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). This variant was predicted to result in … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with LPIN1 -related disorder (PMID: 20583302). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Rhabdomyolysis (present) , Decreased liver function (present) , Abnormal circulating fatty-acid concentration (present) , Elevated circulating creatine kinase concentration (present) , Cardiac arrest (present) , … (more)
Rhabdomyolysis (present) , Decreased liver function (present) , Abnormal circulating fatty-acid concentration (present) , Elevated circulating creatine kinase concentration (present) , Cardiac arrest (present) , Abnormal circulating long-chain fatty-acid concentration (present) , Hepatic steatosis (present) , Renal steatosis (present) , Myocardial steatosis (present) , Ventricular arrhythmia (present) , Skeletal muscle steatosis (present) (less)
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Pathogenic
(Jul 22, 2023)
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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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Invitae
Accession: SCV004344901.1
First in ClinVar: Feb 14, 2024 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: 2444342). 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: 2444342). This premature translational stop signal has been observed in individuals with myoglobinuria (PMID: 20583302, 28986436). This variant is present in population databases (rs778562391, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Gln308Argfs*36) in the LPIN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LPIN1 are known to be pathogenic (PMID: 18817903, 20583302, 22481384, 26111941). (less)
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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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Normal human adipose tissue functions and differentiation in patients with biallelic LPIN1 inactivating mutations. | Pelosi M | Journal of lipid research | 2017 | PMID: 28986436 |
A novel therapeutic approach for LPIN1 mutation-associated rhabdomyolysis--The Austrian experience. | Pichler K | Muscle & nerve | 2015 | PMID: 26111941 |
Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia. | Michot C | Journal of inherited metabolic disease | 2012 | PMID: 22481384 |
LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood. | Michot C | Human mutation | 2010 | PMID: 20583302 |
Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood. | Zeharia A | American journal of human genetics | 2008 | PMID: 18817903 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 20, 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.