rs113817827
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_007078.3(LDB3):c.1606G>A(p.Val536Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,613,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. V536A) has been classified as Uncertain significance.
Frequency
Consequence
NM_007078.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.1606G>A | p.Val536Ile | missense_variant | 10/14 | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.1606G>A | p.Val536Ile | missense_variant | 10/14 | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 152078Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000112 AC: 28AN: 250016Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135394
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461494Hom.: 0 Cov.: 36 AF XY: 0.0000536 AC XY: 39AN XY: 727060
GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152196Hom.: 0 Cov.: 31 AF XY: 0.000255 AC XY: 19AN XY: 74402
ClinVar
Submissions by phenotype
Myofibrillar myopathy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 18, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs113817827, gnomAD 0.07%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 536 of the LDB3 protein (p.Val536Ile). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17327G>A in the primary transcript. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 02, 2023 | The p.V536I variant (also known as c.1606G>A), located in coding exon 9 of the LDB3 gene, results from a G to A substitution at nucleotide position 1606. The valine at codon 536 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort; however, clinical details were limited (Shen C et al. Ann Transl Med, 2022 Feb;10:129). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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 | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Feb 17, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 15, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at