14-23427669-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP2PP3_Strong
The NM_000257.4(MYH7):c.1804A>G(p.Asn602Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. N602S) has been classified as Pathogenic.
Frequency
Consequence
NM_000257.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
The p.Asn602Asp variant in MYH7 has been previously reported in 1 neonate with DCM (Burstein 2014 PMID: 32746448, LMM data). It was absent from large population studies. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. This variant lies in the head region of the protein and missense variants in this region are statistically more likely to be disease-associated (Walsh 2016 PMID: 27532257). In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM1, PM2_Supporting. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at