14-23415475-ATCT-A
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_000257.4(MYH7):c.5186_5188delAGA(p.Lys1729del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MYH7
NM_000257.4 disruptive_inframe_deletion
NM_000257.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.78
Publications
16 publications found
Genes affected
MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]
MHRT (HGNC:51291): (myosin heavy chain associated RNA transcript) This gene encodes a spliced long non-coding RNA that may act as a cardioprotective agent in the heart. Based on a study of a similar gene in mouse, the encoded transcript may regulate chromatin remodeling by acting as a decoy to the BRG1 chromatin repressor complex thus preventing it from binding to its genomic targets. Blocking the actions of BRG1 could be crucial in protecting the heart from pathological hypertrophy. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000257.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 14-23415475-ATCT-A is Pathogenic according to our data. Variant chr14-23415475-ATCT-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 42096.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000257.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MYH7 | MANE Select | c.5186_5188delAGA | p.Lys1729del | disruptive_inframe_deletion | Exon 36 of 40 | NP_000248.2 | P12883 | ||
| MYH7 | c.5186_5188delAGA | p.Lys1729del | disruptive_inframe_deletion | Exon 35 of 39 | NP_001393933.1 | P12883 | |||
| MHRT | n.36_38delTCT | non_coding_transcript_exon | Exon 1 of 6 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MYH7 | TSL:1 MANE Select | c.5186_5188delAGA | p.Lys1729del | disruptive_inframe_deletion | Exon 36 of 40 | ENSP00000347507.3 | P12883 | ||
| MYH7 | c.5231_5233delAGA | p.Lys1744del | disruptive_inframe_deletion | Exon 36 of 40 | ENSP00000528599.1 | ||||
| MYH7 | c.5231_5233delAGA | p.Lys1744del | disruptive_inframe_deletion | Exon 36 of 40 | ENSP00000636014.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461888Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727244
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1461888
Hom.:
AF XY:
AC XY:
0
AN XY:
727244
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112010
Other (OTH)
AF:
AC:
0
AN:
60396
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
4
-
-
MYH7-related skeletal myopathy (4)
-
1
-
Cardiomyopathy (1)
1
-
-
Cardiovascular phenotype (1)
1
-
-
Hypertrophic cardiomyopathy (1)
-
-
-
Congenital myopathy with fiber type disproportion (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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