Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000302024 | SCV000382224 | uncertain significance | Severe combined immunodeficiency due to DCLRE1C deficiency | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV000359181 | SCV000382225 | uncertain significance | DNA ligase IV deficiency | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Gene |
RCV000481605 | SCV000565110 | likely pathogenic | not provided | 2013-09-26 | criteria provided, single submitter | clinical testing | A novel R188Q missense change likely associated with disease was identified in the LIG4 gene. To our knowledge, this variant has neither been published as a pathogenic nor reported as a benign polymorphism. The R188Q missense change was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database indicating it is not a common benign variant in these populations.R188Q represents a non-conservative amino acid substitution, as a positively-charged Arginine residue is replaced with a neutral, polar Glutamine residue. The position in the LIG4 protein where this substitution occurs is highly conserved among species and is located in the DNA-binding domain of the functional protein. Therefore, R188Q is a strong candidate for a pathogenic variant however, the possibility that it is a benign variant cannot be excluded. |
Ambry Genetics | RCV002520852 | SCV003651433 | uncertain significance | Inborn genetic diseases | 2022-11-14 | criteria provided, single submitter | clinical testing | The c.563G>A (p.R188Q) alteration is located in exon 2 (coding exon 1) of the LIG4 gene. This alteration results from a G to A substitution at nucleotide position 563, causing the arginine (R) at amino acid position 188 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |