rs200948763
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003803.4(MYOM1):c.1058C>T(p.Ser353Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S353S) has been classified as Likely benign.
Frequency
Consequence
NM_003803.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOM1 | NM_003803.4 | c.1058C>T | p.Ser353Leu | missense_variant | 7/38 | ENST00000356443.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.1058C>T | p.Ser353Leu | missense_variant | 7/38 | 1 | NM_003803.4 | P2 | |
MYOM1 | ENST00000261606.11 | c.1058C>T | p.Ser353Leu | missense_variant | 7/37 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000442 AC: 11AN: 249126Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135138
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461690Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727130
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74340
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 24, 2023 | The p.S353L variant (also known as c.1058C>T), located in coding exon 6 of the MYOM1 gene, results from a C to T substitution at nucleotide position 1058. The serine at codon 353 is replaced by leucine, an amino acid with 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 | Invitae | Oct 23, 2023 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 353 of the MYOM1 protein (p.Ser353Leu). This variant is present in population databases (rs200948763, gnomAD 0.05%). 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: 570604). 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. 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