chr7-128841530-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_001458.5(FLNC):āc.2084G>Cā(p.Arg695Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,020 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. R695H) has been classified as Likely benign.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.2084G>C | p.Arg695Pro | missense_variant | 13/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.2084G>C | p.Arg695Pro | missense_variant | 13/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.2084G>C | p.Arg695Pro | missense_variant | 13/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.2084G>C | p.Arg695Pro | missense_variant | 13/47 | 1 | A1 | ||
FLNC | ENST00000388853.3 | n.200G>C | non_coding_transcript_exon_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249570Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135398
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461790Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727214
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 08, 2021 | The p.R695P variant (also known as c.2084G>C), located in coding exon 13 of the FLNC gene, results from a G to C substitution at nucleotide position 2084. The arginine at codon 695 is replaced by proline, an amino acid with dissimilar properties. This variant has been detected in a cohort with limb-girdle weakness; however, details were limited (Töpf A et al. Genet Med, 2020 Sep;22:1478-1488). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 | Nov 20, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at