rs1555571267
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_017534.6(MYH2):c.1792G>A(p.Glu598Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MYH2
NM_017534.6 missense
NM_017534.6 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 5.03
Genes affected
MYH2 (HGNC:7572): (myosin heavy chain 2) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in inclusion body myopathy-3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, MYH2
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.1792G>A | p.Glu598Lys | missense_variant | 16/40 | ENST00000245503.10 | |
MYHAS | NR_125367.1 | n.168-30199C>T | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.1792G>A | p.Glu598Lys | missense_variant | 16/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.1792G>A | p.Glu598Lys | missense_variant | 16/40 | 1 | NM_017534.6 | P1 | |
ENST00000399342.6 | n.371-312C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 exome
AF:
AC:
1
AN:
1461894
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
727248
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 01, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 09, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH2 protein function. ClinVar contains an entry for this variant (Variation ID: 499533). This variant has not been reported in the literature in individuals affected with MYH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 598 of the MYH2 protein (p.Glu598Lys). - |
MYH2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 19, 2023 | The MYH2 c.1792G>A variant is predicted to result in the amino acid substitution p.Glu598Lys. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 17, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;.
Sift4G
Uncertain
D;T;T;D
Polyphen
0.0050
.;B;B;.
Vest4
MutPred
Gain of methylation at E598 (P = 0.0044);Gain of methylation at E598 (P = 0.0044);Gain of methylation at E598 (P = 0.0044);Gain of methylation at E598 (P = 0.0044);
MVP
MPC
0.86
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at