rs747978305
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_002471.4(MYH6):c.3529C>T(p.Arg1177Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,587,200 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. R1177G) has been classified as Uncertain significance.
Frequency
Consequence
NM_002471.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.3529C>T | p.Arg1177Trp | missense_variant | 26/39 | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.3529C>T | p.Arg1177Trp | missense_variant | 26/39 | 5 | NM_002471.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000264 AC: 4AN: 151648Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000184 AC: 4AN: 217948Hom.: 0 AF XY: 0.0000167 AC XY: 2AN XY: 119614
GnomAD4 exome AF: 0.0000132 AC: 19AN: 1435552Hom.: 0 Cov.: 34 AF XY: 0.0000112 AC XY: 8AN XY: 712364
GnomAD4 genome ? AF: 0.0000264 AC: 4AN: 151648Hom.: 0 Cov.: 31 AF XY: 0.0000405 AC XY: 3AN XY: 74060
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2019 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported in an individual affected with familial dilated cardiomyopathy (PMID: 20215591). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces arginine with tryptophan at codon 1177 of the MYH6 protein (p.Arg1177Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at