rs747186072
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_017534.6(MYH2):c.3572A>G(p.His1191Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000675 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1191Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_017534.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.3572A>G | p.His1191Arg | missense_variant | 27/40 | ENST00000245503.10 | |
MYHAS | NR_125367.1 | n.168-38675T>C | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.3572A>G | p.His1191Arg | missense_variant | 27/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.3572A>G | p.His1191Arg | missense_variant | 27/40 | 1 | NM_017534.6 | P1 | |
ENST00000399342.6 | n.207-4462T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251416Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135876
GnomAD4 exome AF: 0.0000664 AC: 97AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42AN XY: 727246
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74360
ClinVar
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 15, 2023 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1191 of the MYH2 protein (p.His1191Arg). This variant is present in population databases (rs747186072, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with MYH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 465937). 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. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 15, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2024 | The c.3572A>G (p.H1191R) alteration is located in exon 27 (coding exon 25) of the MYH2 gene. This alteration results from a A to G substitution at nucleotide position 3572, causing the histidine (H) at amino acid position 1191 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at