rs201912847
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001458.5(FLNC):āc.3592G>Cā(p.Val1198Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.3592G>C | p.Val1198Leu | missense_variant | 21/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.3592G>C | p.Val1198Leu | missense_variant | 21/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.3592G>C | p.Val1198Leu | missense_variant | 21/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.3592G>C | p.Val1198Leu | missense_variant | 21/47 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249408Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135334
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461570Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 727126
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 09, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jul 07, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 23, 2019 | Has not been previously reported as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 472042; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31245841) - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 14, 2024 | The p.V1198L variant (also known as c.3592G>C), located in coding exon 21 of the FLNC gene, results from a G to C substitution at nucleotide position 3592. The valine at codon 1198 is replaced by leucine, an amino acid with highly similar properties. 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. Based on the available evidence, the clinical significance of this variant 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 | Dec 09, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at