rs1187923021
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2PP3_Moderate
The ENST00000325888.13(FLNC):āc.7651G>Cā(p.Asp2551His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,016 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 Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2551G) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000325888.13 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.7651G>C | p.Asp2551His | missense_variant | 46/48 | ENST00000325888.13 | NP_001449.3 | |
FLNC-AS1 | NR_149055.1 | n.103-3810C>G | intron_variant, non_coding_transcript_variant | |||||
FLNC | NM_001127487.2 | c.7552G>C | p.Asp2518His | missense_variant | 45/47 | NP_001120959.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.7651G>C | p.Asp2551His | missense_variant | 46/48 | 1 | NM_001458.5 | ENSP00000327145 | P3 | |
FLNC | ENST00000346177.6 | c.7552G>C | p.Asp2518His | missense_variant | 45/47 | 1 | ENSP00000344002 | A1 | ||
FLNC-AS1 | ENST00000469965.1 | n.103-3810C>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461826Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727224
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 02, 2021 | The p.D2551H variant (also known as c.7651G>C), located in coding exon 46 of the FLNC gene, results from a G to C substitution at nucleotide position 7651. The aspartic acid at codon 2551 is replaced by histidine, an amino acid with similar 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 11, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 2551 of the FLNC protein (p.Asp2551His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 539438). 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"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at