ClinVar Miner

Submissions for variant NM_018972.4(GDAP1):c.574C>A (p.Leu192Ile) (rs144199299)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000818255 SCV000958856 uncertain significance Charcot-Marie-Tooth disease, type 4A 2019-08-22 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 192 of the GDAP1 protein (p.Leu192Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is present in population databases (rs144199299, ExAC 0.08%). This variant has not been reported in the literature in individuals with GDAP1-related conditions. 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, Molecular Genetics and Genomics,ARUP Laboratories RCV001286271 SCV001472813 uncertain significance none 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.

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