ClinVar Genomic variation as it relates to human health
NM_000256.3(MYBPC3):c.3782_3792delinsCCTG (p.Glu1261fs)
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_000256.3(MYBPC3):c.3782_3792delinsCCTG (p.Glu1261fs)
Variation ID: 427010 Accession: VCV000427010.3
- Type and length
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Indel, 11 bp
- Location
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Cytogenetic: 11p11.2 11: 47332094-47332104 (GRCh38) [ NCBI UCSC ] 11: 47353645-47353655 (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 22, 2017 Nov 29, 2022 Apr 5, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000256.3:c.3782_3792delAGGCACGGTGTinsCCTG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000256.3:c.3782_3792delinsCCTG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000247.2:p.Glu1261fs frameshift NC_000011.10:g.47332094_47332104delinsCAGG NC_000011.9:g.47353645_47353655delinsCAGG NG_007667.1:g.25599_25609delinsCCTG LRG_386:g.25599_25609delinsCCTG LRG_386t1:c.3782_3792delinsCCTG LRG_386p1:p.Glu1261fs - Protein change
- E1261fs
- Other names
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- Canonical SPDI
- NC_000011.10:47332093:ACACCGTGCCT:CAGG
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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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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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MYBPC3 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3858 | 3875 |
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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Likely pathogenic (2) |
criteria provided, single submitter
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Mar 8, 2016 | RCV000489121.2 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Apr 5, 2016 | RCV002367665.1 |
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
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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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Likely pathogenic
(Mar 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: SCV000577619.3
First in ClinVar: May 22, 2017 Last updated: May 22, 2017 |
Comment:
A c.3782_3792del11insCCTG likely pathogenic variant was identified in the MYBPC3 gene. Although the c.3782_3792del11insCCTG variant has not been reported to our knowledge, this variant causes … (more)
A c.3782_3792del11insCCTG likely pathogenic variant was identified in the MYBPC3 gene. Although the c.3782_3792del11insCCTG variant has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Glutamic acid 1261, changing it to an Alanine, and creating a premature stop codon at position 68 of the new reading frame, denoted p.Glu1261AlafsX68. This variant, occurring in an immunoglobulin-like C2-type domain, replaces the last 14 amino acids with 67 new amino acids, likely disrupting this domain. Other frameshift variants in the MYBPC3 gene resulting in extended protein length or missense/nonsense changes occurring within the last 14 amino acid have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014). Furthermore, the c.3782_3792del11insCCTG variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.Therefore, this variant is likely pathogenic. (less)
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Likely pathogenic
(Apr 05, 2016)
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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: SCV002625778.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The c.3782_3792del11insCCTG variant, located in coding exon 33 of the MYBPC3 gene, results from the deletion of 11 nucleotides and insertion of 4 nucleotides causing … (more)
The c.3782_3792del11insCCTG variant, located in coding exon 33 of the MYBPC3 gene, results from the deletion of 11 nucleotides and insertion of 4 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.E1261Afs*68). This variant results in a frameshift which replaces the last 15 amino acids with 68 aberrant amino acids at the 3' terminus of MYBPC3, elongating the protein. Per ACMG guidelines this variant could be interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med 2008;10:294); however this deletion, insertion and subsequent frameshift occur near the 3' terminus of MYBPC3 and result in the elongation of the protein by 53 amino acids. The exact functional impact of these inserted amino acids is unknown at this time. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6168 samples (12336 alleles) with coverage at this position. Based on the majority of available evidence to date, and since frameshifts are typically deleterious in nature, this alteration is likely to be pathogenic (ACMG Standards and guidelines for the interpretation of sequence variants. Genet Med. 2015;17(5):405-24). (less)
Number of individuals with the variant: 1
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Likely pathogenic
(Nov 13, 2015)
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no assertion criteria provided
Method: provider interpretation
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not provided
Affected status: unknown
Allele origin:
germline
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Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000924850.1
First in ClinVar: Jun 29, 2019 Last updated: Jun 29, 2019 |
Comment:
Genetic testing: The patient had genetic testing for HCM. The test included sequencing of 18 genes associated with HCM: ACTC1, CAV3, GLA, LAMP2, MTTG, MTTI, … (more)
Genetic testing: The patient had genetic testing for HCM. The test included sequencing of 18 genes associated with HCM: ACTC1, CAV3, GLA, LAMP2, MTTG, MTTI, MTTK ,MTTQ, MYBPC3, MYH7, MYL2, MYL3, PRKAG2, TNNC1, TNNI3, TNNT2, TPM1, TTR. Results show that a variant was found: p.Glu1261AlafsX68 (c.3782_3792del11insCCTG) in the MYBPC3 gene. The lab classifies this variant as a variant, likely disease-causing. Given that this variant is a deletion of 11 base pairs and insertion of 4 base pairs, which changes a glutamic acid to an alanine and creates a frameshift that replaces the last 14 amino acids with 67 new amino acids, we consider this variant pathogenic and we feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). This is a novel variant that has not been reported in any previous cases. In total the variant has not been seen in laboratory controls, published controls and individuals from publicly available population datasets. This variant is not listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on 6,157 Caucasian and African American individuals (as of 11/13/15). However, within the same region, there is a missense variant at p.R1263W that is reported as possibly damaging. There are no insertions or deletions within this region in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of 11/13/15). However, there is a missense variant, p.Glu1261Lys that is listed as a variant of uncertain significance. There are no pathogenic variants listed in ClinVar within this region. (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
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 rs1085307897 ...
HelpRecord last updated Nov 29, 2022
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.