1-156137118-G-T
Variant summary
Our verdict is Pathogenic. Variant got 15 ACMG points: 15P and 0B. PS1PM1PM2PP2PP3_StrongPP5_Moderate
The NM_170707.4(LMNA):c.1494G>T(p.Trp498Cys) 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. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin Lovd. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W498R) has been classified as Uncertain significance.
Frequency
Consequence
NM_170707.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LMNA | NM_170707.4 | c.1494G>T | p.Trp498Cys | missense_variant | 9/12 | ENST00000368300.9 | NP_733821.1 | |
LMNA | NM_005572.4 | c.1494G>T | p.Trp498Cys | missense_variant | 9/10 | ENST00000677389.1 | NP_005563.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LMNA | ENST00000368300.9 | c.1494G>T | p.Trp498Cys | missense_variant | 9/12 | 1 | NM_170707.4 | ENSP00000357283.4 | ||
LMNA | ENST00000677389.1 | c.1494G>T | p.Trp498Cys | missense_variant | 9/10 | NM_005572.4 | ENSP00000503633.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Primary familial dilated cardiomyopathy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Feb 17, 2017 | - - |
not provided Other:1
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at