rs758436258
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_000257.4(MYH7):c.5503G>C(p.Glu1835Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,396 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. E1835D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000257.4 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 |
---|---|---|---|---|---|---|---|
MYH7 | NM_000257.4 | c.5503G>C | p.Glu1835Gln | missense_variant | 37/40 | ENST00000355349.4 | |
MYH7 | NM_001407004.1 | c.5503G>C | p.Glu1835Gln | missense_variant | 36/39 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH7 | ENST00000355349.4 | c.5503G>C | p.Glu1835Gln | missense_variant | 37/40 | 1 | NM_000257.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250582Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135564
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460396Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 726596
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Myopathy, myosin storage, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 06, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 11, 2023 | 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 expected to disrupt MYH7 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. ClinVar contains an entry for this variant (Variation ID: 1024639). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is present in population databases (rs758436258, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1835 of the MYH7 protein (p.Glu1835Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at