NM_002470.4(MYH3):c.703A>G (p.Lys235Glu) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 20, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003319957.1

Allele description

NM_002470.4(MYH3):c.703A>G (p.Lys235Glu)

Gene:

MYH3:myosin heavy chain 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_002470.4(MYH3):c.703A>G (p.Lys235Glu)

HGVS:

NC_000017.11:g.10648589T>C
NG_011537.1:g.13710A>G
NM_002470.4:c.703A>GMANE SELECT
NP_002461.2:p.Lys235Glu
NC_000017.10:g.10551906T>C

Protein change:

K235E

Molecular consequence:

NM_002470.4:c.703A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Freeman-Sheldon syndrome (DA2A)
Synonyms:: CRANIOCARPOTARSAL DYSPLASIA; CRANIOCARPOTARSAL DYSTROPHY; WHISTLING FACE-WINDMILL VANE HAND SYNDROME; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008675; MedGen: C0265224; Orphanet: 2053; OMIM: 193700

Name:: Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A (CPSFS1A)
Synonyms:: MULTIPLE PTERYGIUM SYNDROME, AUTOSOMAL DOMINANT; Distal arthrogryposis type 8; Contractures, pterygia, and variable skeletal fusions syndrome 1A
Identifiers:: MONDO: MONDO:0008338; MedGen: C1867440; Orphanet: 65743; OMIM: 178110

Name:: Arthrogryposis, distal, type 2B3
Synonyms:: Arthrogryposis, distal, type 2B3 (Sheldon-Hall)
Identifiers:: MONDO: MONDO:0032751; MedGen: C5193098; OMIM: 618436

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004023395	Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 20, 2023)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004023395

Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 20, 2023)

de novo

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen, SCV004023395.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	not provided	not provided	clinical testing	PubMed (1)

Description

The variant has not been identified in the general population (gnomAD). It has not yet been described in the literature or in the ClinVar and dbSNP151 databases. (as of 07/10/2023) DA2A and DA2B3 underlie heterozygous pathogenic missense variants in the domain of the myosin head and neck in most cases. The alteration was not detected in the patient's parents, so it should be considered a de novo variant. Bioinformatically, the alteration is inconsistently classified as "probably disease-causing" (SIFT) or "benign" (PolyPhen2, mutation Taster). Therfore, the variant has been classified as "likely pathogenic" (ACMG criteria).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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Relating variation to medicine