chr14-23429235-G-C
Variant summary
Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000257.4(MYH7):c.1251C>G(p.Val417Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V417V) has been classified as Likely benign.
Frequency
Consequence
NM_000257.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- dilated cardiomyopathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- dilated cardiomyopathy 1SInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- hypertrophic cardiomyopathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- hypertrophic cardiomyopathy 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- MYH7-related skeletal myopathyInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
- myopathy, myosin storage, autosomal recessiveInheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- myopathy, myosin storage, autosomal dominantInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- congenital myopathy 7A, myosin storage, autosomal dominantInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Ebstein anomalyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hyaline body myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- left ventricular noncompactionInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- arrhythmogenic right ventricular cardiomyopathyInheritance: AD Classification: LIMITED Submitted by: ClinGen
- congenital heart diseaseInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH7 | ENST00000355349.4 | c.1251C>G | p.Val417Val | synonymous_variant | Exon 13 of 40 | 1 | NM_000257.4 | ENSP00000347507.3 | ||
MYH7 | ENST00000713768.1 | c.1251C>G | p.Val417Val | synonymous_variant | Exon 13 of 41 | ENSP00000519070.1 | ||||
MYH7 | ENST00000713769.1 | c.1251C>G | p.Val417Val | synonymous_variant | Exon 12 of 39 | ENSP00000519071.1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152220Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000239 AC: 6AN: 251492 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461868Hom.: 0 Cov.: 34 AF XY: 0.0000275 AC XY: 20AN XY: 727236 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74360 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Benign:2
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Val417Val in exon 13 of MYH7: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1/7020 European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS). Val417Val in exon 13 of MYH7 (allele frequen cy = 1/7020) ** -
Cardiomyopathy Benign:2
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not provided Benign:1
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Hypertrophic cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at