Submissions for variant NM_018972.4(GDAP1):c.693A>T (p.Pro231=) (rs181157785)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000440113	SCV000517055	likely benign	not specified	2015-05-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000643968	SCV000765655	uncertain significance	Charcot-Marie-Tooth disease, type 4A	2020-01-02	criteria provided, single submitter	clinical testing	This sequence change affects codon 231 of the GDAP1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GDAP1 protein. This variant is present in population databases (rs181157785, ExAC 0.02%). This variant has not been reported in the literature in individuals with GDAP1-related disease. ClinVar contains an entry for this variant (Variation ID: 379724). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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	RCV001161258	SCV001323115	uncertain significance	Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive	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.
Illumina Clinical Services Laboratory,Illumina	RCV001161259	SCV001323116	uncertain significance	Charcot-Marie-Tooth disease, recessive intermediate A	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.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173322	SCV001336410	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing