rs267606907
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_002471.4(MYH6):c.2384G>A(p.Arg795Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000294 in 1,461,806 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. R795W) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.2384G>A | p.Arg795Gln | missense_variant | 20/39 | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.2384G>A | p.Arg795Gln | missense_variant | 20/39 | 5 | NM_002471.4 | P1 | |
ENST00000702194.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251344Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135852
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461806Hom.: 0 Cov.: 32 AF XY: 0.0000371 AC XY: 27AN XY: 727208
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy 14 Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 29, 2020 | 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. This variant has been observed in an individual with late-onset hypertrophic cardiomyopathy (PMID: 11815426). ClinVar contains an entry for this variant (Variation ID: 14147). This variant is present in population databases (rs267606907, ExAC 0.02%). This sequence change replaces arginine with glutamine at codon 795 of the MYH6 protein (p.Arg795Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 29, 2002 | - - |
Dilated cardiomyopathy 1EE;C2750467:Hypertrophic cardiomyopathy 14;C3279790:Atrial septal defect 3;C3279791:Sick sinus syndrome 3, susceptibility to;C3495498:Hypertrophic cardiomyopathy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 10, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 08, 2023 | Identified in patients with HCM in published literature (Niimura et al., 2002; Chung et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28518168, 33658040, 33407484, 11815426) - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 29, 2021 | The p.R795Q variant (also known as c.2384G>A), located in coding exon 18 of the MYH6 gene, results from a G to A substitution at nucleotide position 2384. The arginine at codon 795 is replaced by glutamine, an amino acid with highly similar properties. This variant was reported in one individual from a late onset hypertrophic cardiomyopathy (HCM) cohort, as well as in an exome cohort with cardiovascular details not provided (Niimura H et al. Circulation, 2002 Jan;105:446-51; Whiffin N et al. Genet Med, 2017 10;19:1151-1158). This amino acid position is highly conserved in available vertebrate species. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at