NM_001318895.3:c.760T>C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001318895.3(FHL2):āc.760T>Cā(p.Cys254Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001318895.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250418Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135492
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461802Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727210
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74394
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 254 of the FHL2 protein (p.Cys254Arg). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with FHL2-related conditions. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at