MYBPHL

protein-coding

myosin binding protein H like, the group of I-set domain containing|Myosin binding proteins

Gene summary

This gene encodes a protein with two immunoglobulin superfamily domains and a fibronectin 3 domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

MANE transcript

NM_001010985.3

Inheritance

—

ClinVar variants

U:67B:45

Top phenotype

Non-immune hydrops fetalis

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr1:109,292,365-109,307,011

External References & Databases

Ensembl (ENSG00000221986)

Transcript & Mutation Effects

hg38 • Region Span ~14.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial dilated cardiomyopathyLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0016333

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYBPHL variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 118

not providedTotal: 7

Non-immune hydrops fetalisTotal: 1

Primary familial hypertrophic cardiomyopathyTotal: 1

CardiomyopathyTotal: 1

Hypertrophic cardiomyopathyTotal: 1

Long QT syndromeTotal: 1

Brugada syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001010985.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				21 clinvar		21
missense			66 clinvar	22 clinvar		88
nonsense			1 clinvar	2 clinvar		3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	67	45	0	112

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001010985.3	RefSeq	NP_001010985.2	8	MANE Select
ENST00000357155.2	Ensembl	ENSP00000349678.1	8	MANE Select
NM_001265613.2	RefSeq	NP_001252542.1	8	Standard
ENST00000968916.1	Ensembl	ENSP00000638975.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process

Molecular Function

molecular_function
protein binding

Cellular Component

cellular_component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357155
Coding exons: 8
Length: 14677
Individuals with no LoFs: 125365
Homozygous LoFs: 0
Heterozygous LoFs: 383
Defined: 125748
p: 0.00152

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.404	205	222	0.924	0.0000135	2271
Missense (PolyPhen)		54	70.093	0.7704		789
Synonymous	-0.417	95	90.0	1.06	0.00000559	743
Loss of Function	2.32	7	17.5	0.401	8.29e-7	193

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.0017	0.0017	notable
East Asian	0.00016	0.00016	rare
Finnish	0.0031	0.0031	notable
European (Non-Finnish)	0.0021	0.0021	notable
South Asian	0.0010	0.0010	notable
Other	0.0016	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.670
RVIS EVS: 0.6
RVIS percentile EVS: 82.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.172

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium