rs773660161

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002471.4(MYH6):​c.3397A>G​(p.Lys1133Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

MYH6
NM_002471.4 missense

Scores

11
6
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.81
Variant links:
Genes affected
MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYH6NM_002471.4 linkc.3397A>G p.Lys1133Glu missense_variant Exon 26 of 39 ENST00000405093.9 NP_002462.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH6ENST00000405093.9 linkc.3397A>G p.Lys1133Glu missense_variant Exon 26 of 39 5 NM_002471.4 ENSP00000386041.3 P13533

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Uncertain
0.082
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.66
D;D
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.88
D;.
M_CAP
Pathogenic
0.33
D
MetaRNN
Pathogenic
0.88
D;D
MetaSVM
Pathogenic
0.86
D
MutationAssessor
Pathogenic
3.5
H;H
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-2.7
D;D
REVEL
Pathogenic
0.73
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;D
Vest4
0.81
MutPred
0.50
Loss of ubiquitination at K1133 (P = 0.0063);Loss of ubiquitination at K1133 (P = 0.0063);
MVP
0.98
MPC
3.2
ClinPred
0.99
D
GERP RS
4.3
Varity_R
0.64
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs773660161; hg19: chr14-23859601; API