VCV000042684.13 - ClinVar

NM_000256.3(MYBPC3):c.3083C>G (p.Thr1028Ser)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (4)

4 out of 5 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000256.3(MYBPC3):c.3083C>G (p.Thr1028Ser)

Variation ID: 42684 Accession: VCV000042684.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p11.2 11: 47333664 (GRCh38) [ NCBI UCSC ] 11: 47355215 (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	Jan 31, 2015	Mar 7, 2026	Aug 19, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000256.3:c.3083C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000247.2:p.Thr1028Ser	missense
NC_000011.10:g.47333664G>C
NC_000011.9:g.47355215G>C
NG_007667.1:g.24039C>G
LRG_386:g.24039C>G
LRG_386t1:c.3083C>G	LRG_386p1:p.Thr1028Ser
	Q14896:p.Thr1028Ser

... more HGVS ... less HGVS

Protein change

T1028S

Other names

Canonical SPDI

NC_000011.10:47333663:G:C

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.

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Links

ClinGen: CA013420 UniProtKB: Q14896#VAR_045930 dbSNP: rs397516002 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	4727	4749

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.
not specified	Uncertain significance (1)	no assertion criteria provided	Mar 1, 2008	RCV000035557.5
Cardiomyopathy	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Aug 19, 2025	RCV001170190.4
Hypertrophic cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Jan 28, 2022	RCV002513357.5
Cardiovascular phenotype	Uncertain significance (1)	criteria provided, single submitter	Oct 12, 2021	RCV004018754.1

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.	Expand all rows Collapse all rows 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.
Uncertain significance (Oct 12, 2021) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV004938613.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: show The c.3083C>G (p.T1028S) alteration is located in exon 29 (coding exon 29) of the MYBPC3 gene. This alteration results from a C to G substitution at nucleotide position 3083, causing the threonine (T) at amino acid position 1028 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Aug 19, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy	Color Diagnostics, LLC DBA Color Health Accession: SCV007444819.1 First in ClinVar: Feb 15, 2026 Last updated: Feb 15, 2026	Publications: PubMed (4) PubMed: 18403758‚ 24111713‚ 25335496‚ 27532257 Comment: show This missense variant replaces threonine with serine at codon 1028 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 18403758, 24111713, 25335496, 27532257). Two of these probands were children who also carried c.3490+2T>G variant in the same gene in the compound heterozygous state (PMID: 18403758, 25335496). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Platform type: NGS

Uncertain significance (Nov 30, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV001332741.2 First in ClinVar: May 31, 2020 Last updated: Feb 04, 2024	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Jan 28, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Hypertrophic cardiomyopathy	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003248774.4 First in ClinVar: Feb 07, 2023 Last updated: Mar 07, 2026	Publications: PubMed (3) PubMed: 18403758‚ 24111713‚ 27532257 Comment: show This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1028 of the MYBPC3 protein (p.Thr1028Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with MYBPC3-related conditions (PMID: 18403758, 24111713, 27532257). ClinVar contains an entry for this variant (Variation ID: 42684). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Mar 01, 2008) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000059207.4 First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: not provided more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: not provided Number of individuals with the variant: 4

Comment:

The c.3083C>G (p.T1028S) alteration is located in exon 29 (coding exon 29) of the MYBPC3 gene. This alteration results from a C to G substitution at nucleotide position 3083, causing the threonine (T) at amino acid position 1028 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

This missense variant replaces threonine with serine at codon 1028 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 18403758, 24111713, 25335496, 27532257). Two of these probands were children who also carried c.3490+2T>G variant in the same gene in the compound heterozygous state (PMID: 18403758, 25335496). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

Comment:

This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1028 of the MYBPC3 protein (p.Thr1028Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with MYBPC3-related conditions (PMID: 18403758, 24111713, 27532257). ClinVar contains an entry for this variant (Variation ID: 42684). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.	Walsh R	Genetics in medicine : official journal of the American College of Medical Genetics	2017	PMID: 27532257
Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects.	Wessels MW	European journal of human genetics : EJHG	2015	PMID: 25335496
Genetics of hypertrophic cardiomyopathy in Norway.	Berge KE	Clinical genetics	2014	PMID: 24111713
Shared genetic causes of cardiac hypertrophy in children and adults.	Morita H	The New England journal of medicine	2008	PMID: 18403758

Text-mined citations for rs397516002 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Mar 08, 2026