rs121913658
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP3
The ENST00000228841.15(MYL2):c.283C>T(p.Pro95Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P95A) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000228841.15 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYL2 | NM_000432.4 | c.283C>T | p.Pro95Ser | missense_variant | 5/7 | ENST00000228841.15 | NP_000423.2 | |
MYL2 | NM_001406745.1 | c.241C>T | p.Pro81Ser | missense_variant | 4/6 | NP_001393674.1 | ||
MYL2 | NM_001406916.1 | c.226C>T | p.Pro76Ser | missense_variant | 5/7 | NP_001393845.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYL2 | ENST00000228841.15 | c.283C>T | p.Pro95Ser | missense_variant | 5/7 | 1 | NM_000432.4 | ENSP00000228841 | P1 | |
MYL2 | ENST00000548438.1 | c.241C>T | p.Pro81Ser | missense_variant | 4/6 | 3 | ENSP00000447154 | |||
MYL2 | ENST00000663220.1 | c.226C>T | p.Pro76Ser | missense_variant | 5/7 | ENSP00000499568 | ||||
MYL2 | ENST00000549029.1 | n.114C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251488Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461890Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 07, 2023 | ClinVar contains an entry for this variant (Variation ID: 1396446). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with MYL2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 95 of the MYL2 protein (p.Pro95Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at