VCV002507019.1 - ClinVar

NM_000256.3(MYBPC3):c.2778_2781dup (p.Ser928fs)

Germline

Classification

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.

(1)

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000256.3(MYBPC3):c.2778_2781dup (p.Ser928fs)

Variation ID: 2507019 Accession: VCV002507019.1

Type and length

Microsatellite, 4 bp

Location

Cytogenetic: 11p11.2 11: 47335165-47335166 (GRCh38) [ NCBI UCSC ] 11: 47356716-47356717 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Dec 30, 2023	Dec 30, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000256.3:c.2778_2781dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000247.2:p.Ser928fs	frameshift
NC_000011.10:g.47335166TG[5]
NC_000011.9:g.47356717TG[5]
NG_007667.1:g.22532CA[5]
LRG_386:g.22532CA[5]
LRG_386t1:c.2778_2781dup	LRG_386p1:p.Ser928fs

... more HGVS ... less HGVS

Protein change

S928fs

Other names

NM_000256.3:c.2781_2782insCACA

Canonical SPDI

NC_000011.10:47335165:TGTGTG:TGTGTGTGTG

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

mutation affecting reading frame; Sequence Ontology [ SO:1000064]

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

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
Gene	OMIM	HI score Help 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.
MYBPC3		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3971	3990

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.
Hypertrophic cardiomyopathy 4	Pathogenic (1)	criteria provided, single submitter	-	RCV003476887.2

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.
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing, research	Hypertrophic cardiomyopathy 4 (Autosomal dominant inheritance) Affected status: no, unknown, yes, not applicable Allele origin: unknown, paternal, not applicable	Laboratory of Functional Genomics of Cardiovascular Diseases, Federal State Budgetary Institution National Medical Research Centre of Cardiology Named after Academician E.i.chazov. of the Ministry of Health of the Russian Federation Accession: SCV003935995.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023	Observation 1: Clinical Features: Dyspnea (present) , Chest pain (present) , Palpitations (present) , Left ventricular hypertrophy (present) , Left ventricular outflow tract obstruction (present) , Left atrial enlargement … (more) Dyspnea (present) , Chest pain (present) , Palpitations (present) , Left ventricular hypertrophy (present) , Left ventricular outflow tract obstruction (present) , Left atrial enlargement (present) (less) Age: 40-49 years Sex: female Comment on evidence: Apparently, there was a paternal inheritance of disease, since the father of the proband died suddenly at the age of 43 and the proband's mother … (more) Apparently, there was a paternal inheritance of disease, since the father of the proband died suddenly at the age of 43 and the proband's mother has no signs of hypertrophic cardiomyopathy. (less) Observation 2: Clinical Features: Dyspnea (present) , Left ventricular outflow tract obstruction (present) , Left ventricular hypertrophy (present) , Left atrial enlargement (present) Age: 40-49 years Sex: male Observation 3: Clinical Features: Left ventricular diastolic dysfunction (present) , Left atrial enlargement (present) , Mitral valve prolapse (present) Age: 40-49 years Sex: male Observation 4: Age: 10-19 years Sex: female Observation 5: Age: 10-19 years Sex: female Observation 6: Sex: female Tissue: myocardium Result: The levels of mature RNA-transcripts from mutant and wild-type alleles of MYBPC3 gene in total RNA from the proband’s left ventricle (LV) tissue were evaluated using allele-specific expression analysis. Relative level of mutant MYBPC3 RNA was shown to be almost an order of magnitude lower than that of wild-type transcript (0.040 and 0.29, respectively, fold change = 0.14). The total MYBPC3 RNA transcription levels in LV tissue of the proband with HCM and in LV tissue samples of the control group consisting of 14 patients with secondary myocardial hypertrophy were compared. The average MYBPC3 transcript level was about two times lower in proband compared to the control group (0.32 ± 0.05 vs 0.75 ± 0.20, fold change = 0.43). This fact confirms that the mutant allele makes almost no contribution to the total MYBPC3 transcription level and thus causes haploinsufficiency of the gene expression.

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
mutation affecting reading frame (SO:1000064)	Method not provided	The levels of mature RNA-transcripts from mutant and wild-type alleles of MYBPC3 gene in total RNA from the proband’s left ventricle (LV) tissue were evaluated using allele-specific expression analysis. Relative level of mutant MYBPC3 RNA was shown to be almost an order of magnitude lower than that of wild-type transcript (0.040 and 0.29, respectively, fold change = 0.14). The total MYBPC3 RNA transcription levels in LV tissue of the proband with HCM and in LV tissue samples of the control group consisting of 14 patients with secondary myocardial hypertrophy were compared. The average MYBPC3 transcript level was about two times lower in proband compared to the control group (0.32 ± 0.05 vs 0.75 ± 0.20, fold change = 0.43). This fact confirms that the mutant allele makes almost no contribution to the total MYBPC3 transcription level and thus causes haploinsufficiency of the gene expression.	Laboratory of Functional Genomics of Cardiovascular Diseases, Federal State Budgetary Institution National Medical Research Centre of Cardiology Named after Academician E.i.chazov. of the Ministry of Health of the Russian Federation Accession: SCV003935995.1

Citations for germline classification of this variant

There 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 this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_000256.3(MYBPC3):c.2778_2781dup (p.Ser928fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...