rs201104206
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003803.4(MYOM1):c.1978C>T(p.Pro660Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,530 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. P660A) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOM1 | NM_003803.4 | c.1978C>T | p.Pro660Ser | missense_variant | 14/38 | ENST00000356443.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.1978C>T | p.Pro660Ser | missense_variant | 14/38 | 1 | NM_003803.4 | P2 | |
MYOM1 | ENST00000261606.11 | c.1978C>T | p.Pro660Ser | missense_variant | 14/37 | 1 | A2 | ||
MYOM1 | ENST00000577294.1 | n.34C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151944Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249188Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135188
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461586Hom.: 0 Cov.: 30 AF XY: 0.0000536 AC XY: 39AN XY: 727086
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151944Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2AN XY: 74196
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 25, 2021 | This sequence change replaces proline with serine at codon 660 of the MYOM1 protein (p.Pro660Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs201104206, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with MYOM1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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