chr7-128840671-G-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP2PP3BP6BS2
The NM_001458.5(FLNC):c.1673G>T(p.Arg558Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,614,070 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R558H) has been classified as Likely benign.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.1673G>T | p.Arg558Leu | missense_variant | 10/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.1673G>T | p.Arg558Leu | missense_variant | 10/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.1673G>T | p.Arg558Leu | missense_variant | 10/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.1673G>T | p.Arg558Leu | missense_variant | 10/47 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249480Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135386
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461864Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727230
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74342
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 02, 2020 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 05, 2024 | The p.R558L variant (also known as c.1673G>T), located in coding exon 10 of the FLNC gene, results from a G to T substitution at nucleotide position 1673. The arginine at codon 558 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;CN239310:Dilated Cardiomyopathy, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 14, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at