rs368343125
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000356443.9(MYOM1):c.919C>T(p.Arg307Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,232 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. R307P) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000356443.9 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYOM1 | NM_003803.4 | c.919C>T | p.Arg307Cys | missense_variant | 5/38 | ENST00000356443.9 | NP_003794.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.919C>T | p.Arg307Cys | missense_variant | 5/38 | 1 | NM_003803.4 | ENSP00000348821 | P2 | |
MYOM1 | ENST00000261606.11 | c.919C>T | p.Arg307Cys | missense_variant | 5/37 | 1 | ENSP00000261606 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000482 AC: 12AN: 249004Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135094
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461118Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 726820
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74304
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 05, 2023 | The p.R307C variant (also known as c.919C>T), located in coding exon 4 of the MYOM1 gene, results from a C to T substitution at nucleotide position 919. The arginine at codon 307 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 28, 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 MYOM1 protein function. ClinVar contains an entry for this variant (Variation ID: 576075). This variant has not been reported in the literature in individuals affected with MYOM1-related conditions. This variant is present in population databases (rs368343125, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 307 of the MYOM1 protein (p.Arg307Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at