chr14-23407123-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_002471.4(MYH6):c.101G>A(p.Arg34His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R34C) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.101G>A | p.Arg34His | missense_variant | 3/39 | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.101G>A | p.Arg34His | missense_variant | 3/39 | 5 | NM_002471.4 | P1 | |
MYH6 | ENST00000557461.2 | n.168G>A | non_coding_transcript_exon_variant | 3/14 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727248
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74382
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 34 of the MYH6 protein (p.Arg34His). This variant is not present in population databases (gnomAD no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 470502). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 24, 2021 | The MYH6 c.101G>A; p.Arg34His variant (rs762303505), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 470502). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The arginine at codon 34 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.398). However, given the lack of clinical and functional data, the significance of the p.Arg34His variant is uncertain at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at