chr10-68174520-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_032578.4(MYPN):c.2428C>T(p.Arg810Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 in 1,613,968 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R810H) has been classified as Likely benign.
Frequency
Consequence
NM_032578.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.2428C>T | p.Arg810Cys | missense_variant | 11/20 | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.2428C>T | p.Arg810Cys | missense_variant | 11/20 | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251194Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135744
GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461816Hom.: 0 Cov.: 37 AF XY: 0.0000440 AC XY: 32AN XY: 727204
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74326
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1KK Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 810 of the MYPN protein (p.Arg810Cys). This variant is present in population databases (rs369380120, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy (PMID: 30847666). ClinVar contains an entry for this variant (Variation ID: 477751). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2021 | The p.R810C variant (also known as c.2428C>T), located in coding exon 10 of the MYPN gene, results from a C to T substitution at nucleotide position 2428. The arginine at codon 810 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been detected in a non-compaction cardiomyopathy cohort and in an individual with hypertrophic cardiomyopathy; however, clinical details were limited (van Waning JI et al. J. Am. Coll. Cardiol., 2018 Feb;71:711-722; van Lint FHM et al. Neth Heart J. 2019 Jun;27(6):304-309). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at