ClinVar Miner

Submissions for variant NM_018972.4(GDAP1):c.844C>T (p.Arg282Cys) (rs28937906)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235864 SCV000293531 pathogenic not provided 2016-01-11 criteria provided, single submitter clinical testing The R282C pathogenic variant in the GDAP1 gene has been previously reported in association with autosomal recessive CMT in several affected individuals (Nelis et al., 2002; Ammar et al., 2003; Sevilla et al., 2008; Kabzinska et al., 2010). Functional studies show that R282C delays the cell cycle, altering the ability of the GDAP1 protein to interact with its targets (Estela et al., 2011). 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. The R282C variant is a non-conservative amino acid substitution, which alters a position that is conserved across species. Therefore, R282C is interpreted to be a pathogenic variant.
Athena Diagnostics Inc RCV000235864 SCV001144049 pathogenic not provided 2019-03-22 criteria provided, single submitter clinical testing Frequency data from large databases are of low quality and therefore uninformative. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Damaging to protein function(s) relevant to disease mechanism. Strong co-segregation with disease, and data include affected and unaffected individuals from multiple families.
Invitae RCV001235354 SCV001408036 pathogenic Charcot-Marie-Tooth disease, type 4A 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 282 of the GDAP1 protein (p.Arg282Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal recessive Charcot-Marie-Tooth disease (PMID: 12499475, 18812441, 14561495). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4195). This variant has been reported to affect GDAP1 protein function (PMID: 21890626). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004415 SCV000024588 pathogenic Charcot-Marie-Tooth disease, recessive intermediate A 2002-12-24 no assertion criteria provided literature only

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