rs199707920
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PP2PP3_StrongBS2
The NM_001458.5(FLNC):c.3304C>T(p.Pro1102Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.3304C>T | p.Pro1102Ser | missense_variant | 21/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.3304C>T | p.Pro1102Ser | missense_variant | 21/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.3304C>T | p.Pro1102Ser | missense_variant | 21/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.3304C>T | p.Pro1102Ser | missense_variant | 21/47 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000104 AC: 26AN: 249384Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 135346
GnomAD4 exome AF: 0.000247 AC: 361AN: 1461712Hom.: 0 Cov.: 34 AF XY: 0.000232 AC XY: 169AN XY: 727170
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 01, 2023 | Reported in at least one individual with HCM; however, p.(P1102S) was also identified in two control alleles (Gomez et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28356264) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 16, 2020 | - - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Oct 12, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2024 | The p.P1102S variant (also known as c.3304C>T), located in coding exon 21 of the FLNC gene, results from a C to T substitution at nucleotide position 3304. The proline at codon 1102 is replaced by serine, an amino acid with similar properties. This variant has been detected in a hypertrophic cardiomyopathy cohort, but was also detected in controls (Gómez J et al. Circ Cardiovasc Genet, 2017 Apr;10:). 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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at