rs775383465
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PP2PP3_StrongBP6
The NM_001458.5(FLNC):c.4018T>A(p.Phe1340Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,466 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. F1340V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.4018T>A | p.Phe1340Ile | missense_variant | 23/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.4018T>A | p.Phe1340Ile | missense_variant | 23/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.4018T>A | p.Phe1340Ile | missense_variant | 23/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.4018T>A | p.Phe1340Ile | missense_variant | 23/47 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248946Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135160
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461324Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 726978
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 29, 2022 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2023 | The c.4018T>A (p.F1340I) alteration is located in exon 23 (coding exon 23) of the FLNC gene. This alteration results from a T to A substitution at nucleotide position 4018, causing the phenylalanine (F) at amino acid position 1340 to be replaced by an isoleucine (I). Based on insufficient or conflicting 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 | Jul 12, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at