14-23424950-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP2PP3_Moderate
The ENST00000355349.4(MYH7):c.2498A>G(p.Tyr833Cys) variant causes a missense change involving the alteration of a non-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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y833H) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000355349.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH7 | NM_000257.4 | c.2498A>G | p.Tyr833Cys | missense_variant | 22/40 | ENST00000355349.4 | NP_000248.2 | |
MYH7 | NM_001407004.1 | c.2498A>G | p.Tyr833Cys | missense_variant | 21/39 | NP_001393933.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH7 | ENST00000355349.4 | c.2498A>G | p.Tyr833Cys | missense_variant | 22/40 | 1 | NM_000257.4 | ENSP00000347507 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 21, 2013 | The Tyr833Cys variant in MYH7 has not been reported in individuals with cardiomy opathy or in large population studies. Tyrosine (Tyr) at position 833 is not ful ly conserved as some mammals and other evolutionarily distant species carry a ph enylalanine (Phe), which raises the possibility that a change at this position m ay be tolerated. However, the change to cysteine (Cys) was predicted to be patho genic using a computational tool clinically validated by our laboratory. This to ol's pathogenic prediction is estimated to be correct 94% of the time (Jordan 20 11). In summary, additional information is needed to fully assess the clinical s ignificance of the Tyr833Cys variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at