14-23390407-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_002471.4(MYH6):c.3382C>T(p.Arg1128Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,611,090 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. R1128H) has been classified as Uncertain significance.
Frequency
Consequence
NM_002471.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.3382C>T | p.Arg1128Cys | missense_variant | 26/39 | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.3382C>T | p.Arg1128Cys | missense_variant | 26/39 | 5 | NM_002471.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151922Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459168Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 725974
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151922Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74194
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 24, 2014 | The Arg1128Cys variant in MYH6 has not been previously reported in individuals w ith cardiomyopathy. Data from large population studies is insufficient to assess the frequency of this variant. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this informati on is not predictive enough to determine pathogenicity. In summary, the clinical significance of the Arg1128Cys variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at