Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000237016 | SCV000293773 | uncertain significance | not provided | 2016-01-11 | criteria provided, single submitter | clinical testing | The L329F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the L329F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV001049793 | SCV001213864 | uncertain significance | Charcot-Marie-Tooth disease type 4A | 2019-11-27 | criteria provided, single submitter | clinical testing | 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with GDAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 246290). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 329 of the GDAP1 protein (p.Leu329Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. |