rs376653815
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 7P and 1B. PM2PP2PP3_StrongBP6
The NM_001458.5(FLNC):c.5777A>G(p.Tyr1926Cys) 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. 12/21 in silico tools predict a damaging 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. Y1926D) 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 Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.5777A>G | p.Tyr1926Cys | missense_variant | 35/48 | ENST00000325888.13 | |
FLNC-AS1 | NR_149055.1 | n.216-63T>C | intron_variant, non_coding_transcript_variant | ||||
FLNC | NM_001127487.2 | c.5678A>G | p.Tyr1893Cys | missense_variant | 34/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.5777A>G | p.Tyr1926Cys | missense_variant | 35/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.5678A>G | p.Tyr1893Cys | missense_variant | 34/47 | 1 | A1 | ||
FLNC-AS1 | ENST00000469965.1 | n.216-63T>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251178Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135832
GnomAD4 exome Cov.: 34
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2020 | The p.Y1926C variant (also known as c.5777A>G), located in coding exon 35 of the FLNC gene, results from an A to G substitution at nucleotide position 5777. The tyrosine at codon 1926 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, 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 | Mar 09, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at