18-3164337-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003803.4(MYOM1):c.1442C>G(p.Thr481Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T481I) has been classified as Uncertain significance.
Frequency
Consequence
NM_003803.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOM1 | NM_003803.4 | c.1442C>G | p.Thr481Arg | missense_variant | 10/38 | ENST00000356443.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.1442C>G | p.Thr481Arg | missense_variant | 10/38 | 1 | NM_003803.4 | P2 | |
MYOM1 | ENST00000261606.11 | c.1442C>G | p.Thr481Arg | missense_variant | 10/37 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246234Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133494
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460356Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 726274
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74390
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 05, 2022 | The c.1442C>G (p.T481R) alteration is located in exon 10 (coding exon 9) of the MYOM1 gene. This alteration results from a C to G substitution at nucleotide position 1442, causing the threonine (T) at amino acid position 481 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces threonine with arginine at codon 481 of the MYOM1 protein (p.Thr481Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MYOM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 239568). 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