7-128850388-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001458.5(FLNC):āc.5303C>Gā(p.Thr1768Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.5303C>G | p.Thr1768Arg | missense_variant | Exon 32 of 48 | ENST00000325888.13 | NP_001449.3 | |
FLNC | NM_001127487.2 | c.5204C>G | p.Thr1735Arg | missense_variant | Exon 31 of 47 | NP_001120959.1 | ||
FLNC-AS1 | NR_149055.1 | n.333G>C | non_coding_transcript_exon_variant | Exon 4 of 4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.5303C>G | p.Thr1768Arg | missense_variant | Exon 32 of 48 | 1 | NM_001458.5 | ENSP00000327145.8 | ||
FLNC | ENST00000346177.6 | c.5204C>G | p.Thr1735Arg | missense_variant | Exon 31 of 47 | 1 | ENSP00000344002.6 | |||
FLNC-AS1 | ENST00000469965.1 | n.333G>C | non_coding_transcript_exon_variant | Exon 4 of 4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249398Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135316
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461422Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727042
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74382
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
The p.T1768R variant (also known as c.5303C>G), located in coding exon 32 of the FLNC gene, results from a C to G substitution at nucleotide position 5303. The threonine at codon 1768 is replaced by arginine, an amino acid with similar properties. This amino acid position is conserved. 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
This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 1768 of the FLNC protein (p.Thr1768Arg). This variant is present in population databases (rs778860499, gnomAD 0.002%). 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: 943920). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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