Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000227222 | SCV000291964 | uncertain significance | not provided | 2017-08-09 | criteria provided, single submitter | clinical testing | The D455G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The NHLBI Exome Sequencing Project reports D455G was observed in 12/4406 (0.3%) alleles from individuals of African American background, and and the 1000 Genomes Project reports D455G was observed in 3/1322 (0.2%) alleles from individuals of African background. The D455G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and Aspartic acid has been seen at this position in evolution. Additionally, in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000227222 | SCV001009205 | likely benign | not provided | 2024-01-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002461023 | SCV002754784 | uncertain significance | Inborn genetic diseases | 2020-03-04 | criteria provided, single submitter | clinical testing | The p.D455G variant (also known as c.1364A>G), located in coding exon 12 of the IKBKAP gene, results from an A to G substitution at nucleotide position 1364. The aspartic acid at codon 455 is replaced by glycine, an amino acid with similar properties. 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. |
St. |
RCV003230264 | SCV003928107 | uncertain significance | Medulloblastoma | 2023-04-14 | criteria provided, single submitter | clinical testing | The ELP1 c.1364A>G (p.Asp455Gly) missense change has a maximum subpopulation frequency of 0.23% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with medulloblastoma or familial dysautonomia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Mayo Clinic Laboratories, |
RCV000227222 | SCV004225076 | uncertain significance | not provided | 2022-08-03 | criteria provided, single submitter | clinical testing | BP4 |
Natera, |
RCV001276239 | SCV001462241 | likely benign | Familial dysautonomia | 2020-01-02 | no assertion criteria provided | clinical testing |