rs369250297
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PP2PP3_ModerateBP6BS2
The NM_001458.5(FLNC):c.6923C>T(p.Pro2308Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,611,406 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). Synonymous variant affecting the same amino acid position (i.e. P2308P) has been classified as Likely benign.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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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.6923C>T | p.Pro2308Leu | missense_variant | 41/48 | ENST00000325888.13 | |
FLNC-AS1 | NR_149055.1 | n.103-1211G>A | intron_variant, non_coding_transcript_variant | ||||
FLNC | NM_001127487.2 | c.6824C>T | p.Pro2275Leu | missense_variant | 40/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.6923C>T | p.Pro2308Leu | missense_variant | 41/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.6824C>T | p.Pro2275Leu | missense_variant | 40/47 | 1 | A1 | ||
FLNC-AS1 | ENST00000469965.1 | n.103-1211G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000414 AC: 10AN: 241588Hom.: 0 AF XY: 0.0000303 AC XY: 4AN XY: 131844
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1459166Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 725754
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 03, 2021 | Identified in a patient with dilated cardiomyopathy in the published literature (Ader et al., 2018); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 472152; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect This variant is associated with the following publications: (PMID: 30418145) - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 14, 2023 | The p.P2308L variant (also known as c.6923C>T), located in coding exon 41 of the FLNC gene, results from a C to T substitution at nucleotide position 6923. The proline at codon 2308 is replaced by leucine, an amino acid with similar properties. This alteration has been detected in individuals reported to have cardiomyopathy; however, details were limited (Ader F et al. Med Sci (Paris), 2018 Nov;34 Hors série n°2:39-41; Smith E et al. J Am Heart Assoc. 2022 May;11(9):e024501). This amino acid position is highly 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 | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at