Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000351953 | SCV000474457 | uncertain significance | Hypogonadotropic hypogonadism 5 with or without anosmia | 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 |
RCV000483542 | SCV000570549 | uncertain significance | not provided | 2016-06-02 | criteria provided, single submitter | clinical testing | The D1878G variant in the CHD7 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D1878G variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D1878G 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. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. As an alternate mechanism, this variant (c.5633 A>G) is predicted to create a cryptic donor site upstream of the canonical donor splice site of intron 28, which may cause abnormal splicing. However, in the absence of RNA/functional studies, the actual effect of c.5633 A>G in this individual is unknown. We interpret D1878G as a variant of uncertain significance. |
| Invitae | RCV000311193 | SCV001405840 | likely benign | CHARGE association | 2022-08-31 | criteria provided, single submitter | clinical testing |