Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001048938 | SCV001212968 | uncertain significance | Charcot-Marie-Tooth disease type 4A | 2023-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 347 of the GDAP1 protein (p.Met347Val). This variant is present in population databases (rs112786851, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GDAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 845803). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Illumina Laboratory Services, |
RCV001162810 | SCV001324777 | uncertain significance | Charcot-Marie-Tooth disease recessive intermediate A | 2018-01-12 | 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, |
RCV001162811 | SCV001324778 | uncertain significance | Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive | 2018-01-12 | 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. |
Ambry Genetics | RCV002393240 | SCV002700684 | uncertain significance | Inborn genetic diseases | 2020-11-03 | criteria provided, single submitter | clinical testing | The p.M347V variant (also known as c.1039A>G), located in coding exon 6 of the GDAP1 gene, results from an A to G substitution at nucleotide position 1039. The methionine at codon 347 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and valine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of axonal Charcot-Marie-Tooth disease, type 2K (CMT2K); however, its contribution to the development of autosomal recessive Charcot-Marie-Tooth disease is uncertain. |
Gene |
RCV003156305 | SCV003845560 | uncertain significance | not provided | 2023-03-19 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |