rs199804244
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP6BS1BS2
The NM_001458.5(FLNC):c.3938G>A(p.Arg1313Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000409 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R1313G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.3938G>A | p.Arg1313Gln | missense_variant | 22/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.3938G>A | p.Arg1313Gln | missense_variant | 22/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.3938G>A | p.Arg1313Gln | missense_variant | 22/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.3938G>A | p.Arg1313Gln | missense_variant | 22/47 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000362 AC: 55AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000205 AC: 51AN: 249112Hom.: 0 AF XY: 0.000222 AC XY: 30AN XY: 135262
GnomAD4 exome AF: 0.000414 AC: 605AN: 1461776Hom.: 0 Cov.: 34 AF XY: 0.000419 AC XY: 305AN XY: 727198
GnomAD4 genome ? AF: 0.000362 AC: 55AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.000431 AC XY: 32AN XY: 74314
ClinVar
Submissions by phenotype
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | FLNC NM_001458.4 exon 22 p.Arg1313Gln (c.3938G>A): This variant has not been reported in the literature and is present in 0.04% (51/128340) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/7-128486191-G-A). This variant is present in ClinVar (Variation ID:472052). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 16, 2024 | The p.R1313Q variant (also known as c.3938G>A), located in coding exon 22 of the FLNC gene, results from a G to A substitution at nucleotide position 3938. The arginine at codon 1313 is replaced by glutamine, an amino acid with highly similar properties. This variant was reported in a congenital heart disease exome testing cohort; however, clinical details were limited (Watkins WS et al. Nat Commun, 2019 10;10:4722). 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 07, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | FLNC: BP4, BS2 - |
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 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at