ClinVar Genomic variation as it relates to human health
NM_003476.5(CSRP3):c.286_287del (p.Pro96fs)
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.
Pathogenic(1); Uncertain significance(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_003476.5(CSRP3):c.286_287del (p.Pro96fs)
Variation ID: 1284733 Accession: VCV001284733.11
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 11p15.1 11: 19186343-19186344 (GRCh38) [ NCBI UCSC ] 11: 19207890-19207891 (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 Sep 25, 2021 Feb 28, 2024 Jul 3, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003476.5:c.286_287del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003467.1:p.Pro96fs frameshift NM_001369404.1:c.117_118del NP_001356333.1:p.Gln40fs frameshift NC_000011.10:g.19186345_19186346del NC_000011.9:g.19207892_19207893del NG_011932.2:g.29230_29231del LRG_440:g.29230_29231del LRG_440t1:c.286_287del - Protein change
- P96fs, Q40fs
- Other names
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- Canonical SPDI
- NC_000011.10:19186342:GGGG:GG
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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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CSRP3 | - | - |
GRCh38 GRCh37 |
407 | 444 |
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
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
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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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Uncertain significance (3) |
criteria provided, single submitter
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Nov 15, 2021 | RCV001700909.6 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jul 3, 2023 | RCV001868384.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 7, 2021 | RCV002440839.1 |
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
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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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Uncertain significance
(Nov 15, 2021)
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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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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002502276.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 2
Secondary finding: no
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Uncertain significance
(Jul 07, 2021)
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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: SCV002752791.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The c.286_287delCC variant, located in coding exon 3 of the CSRP3 gene, results from a deletion of two nucleotides at nucleotide positions 286 to 287, … (more)
The c.286_287delCC variant, located in coding exon 3 of the CSRP3 gene, results from a deletion of two nucleotides at nucleotide positions 286 to 287, causing a translational frameshift with a predicted alternate stop codon (p.P96Kfs*35). This variant was reported in a sudden infant death case with an additional cardiac variant detected and limited clinical information provided (Tester DJ et al. J. Am. Coll. Cardiol., 2018 Mar;71:1217-1227). This variant was also detected in an individual reported to have hypertrophic cardiomyopathy; however, details were limited (van Lint FHM et al. Neth Heart J. 2019 Jun;27(6):304-309). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of CSRP3 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Aug 11, 2021)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1M
Hypertrophic cardiomyopathy 12
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002793766.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jul 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 12
Dilated cardiomyopathy 1M
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002264599.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Pro96Lysfs*35) in the CSRP3 gene. It … (more)
For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Pro96Lysfs*35) in the CSRP3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CSRP3 are known to be pathogenic (PMID: 12642359, 14567970, 16352453, 20087448, 34558151). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy and/or sudden infant death syndrome (PMID: 29544605, 30847666; Invitae). ClinVar contains an entry for this variant (Variation ID: 1284733). (less)
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Uncertain significance
(-)
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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: SCV001925912.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
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Uncertain significance
(-)
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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: SCV001929153.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 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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CSRP3, p.Arg122*, is responsible for hypertrophic cardiomyopathy in a Chinese family. | Huang H | The journal of gene medicine | 2022 | PMID: 34558151 |
Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance. | van Lint FHM | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2019 | PMID: 30847666 |
Cardiac Genetic Predisposition in Sudden Infant Death Syndrome. | Tester DJ | Journal of the American College of Cardiology | 2018 | PMID: 29544605 |
Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity? | van Rijsingen IA | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2009 | PMID: 20087448 |
Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle LIM protein, and telethonin. | Bos JM | Molecular genetics and metabolism | 2006 | PMID: 16352453 |
Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis. | Mohapatra B | Molecular genetics and metabolism | 2003 | PMID: 14567970 |
Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy. | Geier C | Circulation | 2003 | PMID: 12642359 |
Text-mined citations for rs960577385 ...
HelpRecord last updated Mar 05, 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.