11-47332244-C-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_000256.3(MYBPC3):c.3642G>T(p.Trp1214Cys) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W1214R) has been classified as Pathogenic.
Frequency
Consequence
NM_000256.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.3642G>T | p.Trp1214Cys | missense_variant | Exon 33 of 35 | 5 | NM_000256.3 | ENSP00000442795.1 | ||
MYBPC3 | ENST00000399249.6 | c.3642G>T | p.Trp1214Cys | missense_variant | Exon 32 of 34 | 5 | ENSP00000382193.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy 1 Uncertain:1
The MYBPC3 Trp1214Cys variant was identified by our laboratory in a 57 year old male, diagnosed with hypertrophic cardiomyopathy (HCM) at 42 years. The proband has no family history of HCM. This variant is absent the 1000 genomes project (http://www.1000genomes.org/), as well as the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). In silico tools SIFT, MutationTaster, PolyPhen-HCM and PolyPhen-2 predict that is variant to be deleterious. Additional evidence is required to further elucidate the role of this variant in disease or as a normal variation. In summary, based on this information we classify MYBPC3 Trp1214Cys as a variant of "uncertain significance". -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at