Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000818255 | SCV000958856 | uncertain significance | Charcot-Marie-Tooth disease type 4A | 2022-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 192 of the GDAP1 protein (p.Leu192Ile). This variant is present in population databases (rs144199299, gnomAD 0.1%). 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: 660950). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
ARUP Laboratories, |
RCV001811503 | SCV001472813 | uncertain significance | not provided | 2019-12-18 | criteria provided, single submitter | clinical testing | The GDAP1 c.574C>A; p.Leu192Ile variant (rs144199299), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 660950). This variant is found in the African population with an overall allele frequency of 0.12% (30/24878 alleles) in the Genome Aggregation Database. The leucine at codon 192 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Leu192Ile variant is uncertain at this time. |
Ambry Genetics | RCV002345879 | SCV002648554 | uncertain significance | Inborn genetic diseases | 2020-10-21 | criteria provided, single submitter | clinical testing | The p.L192I variant (also known as c.574C>A), located in coding exon 4 of the GDAP1 gene, results from a C to A substitution at nucleotide position 574. The leucine at codon 192 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |