7-128838321-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_001458.5(FLNC):c.1102G>A(p.Val368Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,970 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. V368L) has been classified as Uncertain significance.
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.1102G>A | p.Val368Met | missense_variant | 7/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.1102G>A | p.Val368Met | missense_variant | 7/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.1102G>A | p.Val368Met | missense_variant | 7/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.1102G>A | p.Val368Met | missense_variant | 7/47 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249550Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135396
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461750Hom.: 0 Cov.: 34 AF XY: 0.0000275 AC XY: 20AN XY: 727180
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 13, 2023 | Identified in a proband and father with HCM in published literature; however, it is unclear whether these individuals harbored additional cardiogenetic variants (PMID: 36286284); 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: 36286284) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 07, 2023 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2022 | The p.V368M variant (also known as c.1102G>A), located in coding exon 7 of the FLNC gene, results from a G to A substitution at nucleotide position 1102. The valine at codon 368 is replaced by methionine, an amino acid with highly similar properties. 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 05, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at