Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic Diagnostics, |
RCV000339279 | SCV000341992 | uncertain significance | not provided | 2017-05-05 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000261037 | SCV000476419 | uncertain significance | Dilated cardiomyopathy 1X | 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 Clinical Services Laboratory, |
RCV000318693 | SCV000476420 | uncertain significance | Fukuyama congenital muscular dystrophy | 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. |
Invitae | RCV000465197 | SCV000546096 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2019-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 125 of the FKTN protein (p.Gly125Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs142783718, ExAC 0.02%). This variant has been reported in an infant affected with anophthalmia/microphthalmia or coloboma (PMID: 26130484). ClinVar contains an entry for this variant (Variation ID: 288016). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and in an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV000617672 | SCV000737183 | uncertain significance | Cardiovascular phenotype | 2020-09-29 | criteria provided, single submitter | clinical testing | The p.G125V variant (also known as c.374G>T), located in coding exon 4 of the FKTN gene, results from a G to T substitution at nucleotide position 374. The glycine at codon 125 is replaced by valine, an amino acid with dissimilar 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. |