chr14-23388214-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_002471.4(MYH6):c.4300G>A(p.Val1434Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,350 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V1434V) has been classified as Likely benign.
Frequency
Consequence
NM_002471.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.4300G>A | p.Val1434Ile | missense_variant | 30/39 | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.4300G>A | p.Val1434Ile | missense_variant | 30/39 | 5 | NM_002471.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251466Hom.: 1 AF XY: 0.0000441 AC XY: 6AN XY: 135904
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460104Hom.: 1 Cov.: 35 AF XY: 0.0000151 AC XY: 11AN XY: 726358
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74376
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 | Dec 23, 2011 | The Val1434Ile variant (MYH6) has not been previously reported nor previously id entified by our laboratory. Valine (Val) at position 1434 is moderately conserve d in evolutionarily distant species (frog carries a leucine), and this informati on is insufficient to predict if a change would impact the protein. Computationa l predictions on the impact to the protein are mixed (PolyPhen2 = benign, SIFT = pathogenic), though the accuracy of these tools is unknown. Additional informat ion is needed to fully assess the clinical significance of the Val1434Ile varian t. - |
Hypertrophic cardiomyopathy 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2021 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 44508). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs397516769, ExAC 0.01%). This sequence change replaces valine with isoleucine at codon 1434 of the MYH6 protein (p.Val1434Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. - |
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 | Aug 20, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at