NM_020433.5:c.497T>G
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B.
The NM_020433.5(JPH2):c.497T>G(p.Leu166Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L166L) has been classified as Likely benign.
Frequency
Consequence
NM_020433.5 missense
Scores
Clinical Significance
Conservation
Publications
- hypertrophic cardiomyopathy 17Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
- cardiomyopathy, dilated, 2EInheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- hypertrophic cardiomyopathyInheritance: AD Classification: MODERATE Submitted by: ClinGen
- dilated cardiomyopathyInheritance: SD Classification: MODERATE Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Leu166Arg variant in JPH2 has not been previously reported in individuals with cardiomyopathy. Data from large population studies is insufficient to asses s the frequency of this variant. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this informat ion is not predictive enough to determine pathogenicity. In summary, the clinica l significance of the p.Leu166Arg variant is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at