ClinVar Miner

Submissions for variant NM_020631.5(PLEKHG5):c.719A>G (p.Asp240Gly) (rs199794578)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724237 SCV000232768 uncertain significance not provided 2014-11-14 criteria provided, single submitter clinical testing
GeneDx RCV000724237 SCV000279364 likely benign not provided 2021-05-07 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
Invitae RCV000546292 SCV000646063 uncertain significance Distal spinal muscular atrophy, autosomal recessive 4; Charcot-Marie-Tooth disease, recessive intermediate c 2020-10-29 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 240 of the PLEKHG5 protein (p.Asp240Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs199794578, ExAC 0.1%). This variant has not been reported in the literature in individuals with PLEKHG5-related disease. ClinVar contains an entry for this variant (Variation ID: 198894). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly 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.
Illumina Clinical Services Laboratory,Illumina RCV001098160 SCV001254508 uncertain significance Distal spinal muscular atrophy, autosomal recessive 4 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000724237 SCV001713778 uncertain significance not provided 2019-04-14 criteria provided, single submitter clinical testing
Clinical Genetics,Academic Medical Center RCV000724237 SCV001920949 uncertain significance not provided no assertion criteria provided clinical testing

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