Intellectual disability
Gene: MYH10 Green List (high evidence)Green List (high evidence)
The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.Created: 3 May 2024, 11:55 a.m. | Last Modified: 3 May 2024, 11:55 a.m.
Panel Version: 6.11
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Green List (high evidence)
Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.Created: 19 Dec 2023, 12:31 p.m. | Last Modified: 19 Dec 2023, 12:31 p.m.
Panel Version: 5.351
16 individuals were identified with heterozygous MYH10 variants and they presented with a broad spectrum of neurodevelopmental disorders and variable congenital anomalies that affect most organ systems. These phenotypes were recapitulated in animal models of altered MYH10 activity. 11 of these 16 patients had global developmental delay and/ or intellectual disability.
This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.Created: 19 Dec 2023, 12:27 p.m. | Last Modified: 19 Dec 2023, 12:27 p.m.
Panel Version: 5.347
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Publications
Red List (low evidence)
Comment on mode of inheritance: This is a possible DD gene in Gene2Phenotype for MYH10-related Multiple congenital anomalies, where the MOI has been assignedCreated: 26 Feb 2018, 11:57 a.m.
Currently there is not enough evidence to support this gene being upgraded from the Red ratingCreated: 26 Feb 2018, 11:55 a.m.
Comment on phenotypes: To date there is no OMIM gene-phenotype as this has not been confirmed since both of the reported cases (PMID:25003005, 24901346,25356899) the variants have been classified as a variant of unknown significance because its contribution to a complex neurologic phenotype has not been confirmed.Created: 26 Feb 2018, 11:54 a.m.
Comment on publications: added publications to support the association to ID phenotypeCreated: 26 Feb 2018, 11:50 a.m.
Tag gene-checked tag was added to gene: MYH10.
Tag Q4_23_promote_green was removed from gene: MYH10.
Source Expert Review Green was added to MYH10. Source NHS GMS was added to MYH10. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: myh10 has been classified as Amber List (Moderate Evidence).
Tag Q4_23_promote_green tag was added to gene: MYH10.
Phenotypes for gene: MYH10 were changed from Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; MYH10-related Multiple congenital anomalies to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; MYH10-related Multiple congenital anomalies
Phenotypes for gene: MYH10 were changed from MYH10-related Multiple congenital anomalies, Intellectual disability to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; MYH10-related Multiple congenital anomalies
Publications for gene: MYH10 were set to 25356899; 25003005
Mode of inheritance for gene: MYH10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
MYH10 was added to Intellectual disability panel. Sources: Gene2Phenotype
MYH10 was created by Ellen McDonagh
If promoting or demoting a gene, please provide comments to justify a decision to move it.
Genes included in a Genomics England gene panel for a rare disease category (green list) should fit the criteria A-E outlined below.
These guidelines were developed as a combination of the ClinGen DEFINITIVE evidence for a causal role of the gene in the disease(a), and the Developmental Disorder Genotype-Phenotype (DDG2P) CONFIRMED DD Gene evidence level(b) (please see the original references provided below for full details). These help provide a guideline for expert reviewers when assessing whether a gene should be on the green or the red list of a panel.
A. There are plausible disease-causing mutations(i) within, affecting or encompassing an interpretable functional region(ii) of this gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
B. There are plausible disease-causing mutations(i) within, affecting or encompassing cis-regulatory elements convincingly affecting the expression of a single gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
C. As definitions A or B but in 2 or 3 unrelated cases/families with the phenotype, with the addition of convincing bioinformatic or functional evidence of causation e.g. known inborn error of metabolism with mutation in orthologous gene which is known to have the relevant deficient enzymatic activity in other species; existence of an animal model which recapitulates the human phenotype.
AND
D. Evidence indicates that disease-causing mutations follow a Mendelian pattern of causation appropriate for reporting in a diagnostic setting(iv).
AND
E. No convincing evidence exists or has emerged that contradicts the role of the gene in the specified phenotype.
(i)Plausible disease-causing mutations: Recurrent de novo mutations convincingly affecting gene function. Rare, fully-penetrant mutations - relevant genotype never, or very rarely, seen in controls. (ii) Interpretable functional region: ORF in protein coding genes miRNA stem or loop. (iii) Phenotype: the rare disease category, as described in the eligibility statement. (iv) Intermediate penetrance genes should not be included.
It’s assumed that loss-of-function variants in this gene can cause the disease/phenotype unless an exception to this rule is known. We would like to collect information regarding exceptions. An example exception is the PCSK9 gene, where loss-of-function variants are not relevant for a hypercholesterolemia phenotype as they are associated with increased LDL-cholesterol uptake via LDLR (PMID: 25911073).
If a curated set of known-pathogenic variants is available for this gene-phenotype, please contact us at [email protected]
We classify loss-of-function variants as those with the following Sequence Ontology (SO) terms:
Term descriptions can be found on the PanelApp homepage and Ensembl.
If you are submitting this evaluation on behalf of a clinical laboratory please indicate whether you report variants in this gene as part of your current diagnostic practice by checking the box
Standardised terms were used to represent the gene-disease mode of inheritance, and were mapped to commonly used terms from the different sources. Below each of the terms is described, along with the equivalent commonly-used terms.
A variant on one allele of this gene can cause the disease, and imprinting has not been implicated.
A variant on the paternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on the maternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on one allele of this gene can cause the disease. This is the default used for autosomal dominant mode of inheritance where no knowledge of the imprinting status of the gene required to cause the disease is known. Mapped to the following commonly used terms from different sources: autosomal dominant, dominant, AD, DOMINANT.
A variant on both alleles of this gene is required to cause the disease. Mapped to the following commonly used terms from different sources: autosomal recessive, recessive, AR, RECESSIVE.
The disease can be caused by a variant on one or both alleles of this gene. Mapped to the following commonly used terms from different sources: autosomal recessive or autosomal dominant, recessive or dominant, AR/AD, AD/AR, DOMINANT/RECESSIVE, RECESSIVE/DOMINANT.
A variant on one allele of this gene can cause the disease, however a variant on both alleles of this gene can result in a more severe form of the disease/phenotype.
A variant in this gene can cause the disease in males as they have one X-chromosome allele, whereas a variant on both X-chromosome alleles is required to cause the disease in females. Mapped to the following commonly used term from different sources: X-linked recessive.
A variant in this gene can cause the disease in males as they have one X-chromosome allele. A variant on one allele of this gene may also cause the disease in females, though the disease/phenotype may be less severe and may have a later-onset than is seen in males. X-linked inactivation and mosaicism in different tissues complicate whether a female presents with the disease, and can change over their lifetime. This term is the default setting used for X-linked genes, where it is not known definitately whether females require a variant on each allele of this gene in order to be affected. Mapped to the following commonly used terms from different sources: X-linked dominant, x-linked, X-LINKED, X-linked.
The gene is in the mitochondrial genome and variants within this can cause this disease, maternally inherited. Mapped to the following commonly used term from different sources: Mitochondrial.
Mapped to the following commonly used terms from different sources: Unknown, NA, information not provided.
For example, if the mode of inheritance is digenic, please indicate this in the comments and which other gene is involved.