rs370177143
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003803.4(MYOM1):c.1442C>T(p.Thr481Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. T481R) has been classified as Uncertain significance.
Frequency
Consequence
NM_003803.4 missense
Scores
Clinical Significance
Conservation
Publications
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.1442C>T | p.Thr481Ile | missense_variant | Exon 10 of 38 | 1 | NM_003803.4 | ENSP00000348821.4 | ||
MYOM1 | ENST00000261606.11 | c.1442C>T | p.Thr481Ile | missense_variant | Exon 10 of 37 | 1 | ENSP00000261606.7 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Uncertain:1
This variant has not been reported in the literature in individuals affected with MYOM1-related conditions. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 481 of the MYOM1 protein (p.Thr481Ile). This variant is not present in population databases (gnomAD no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at