ClinVar Miner

Submissions for variant NM_001303256.3(MORC2):c.754C>T (p.Arg252Trp) (rs864309503)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000202547 SCV000655834 pathogenic Charcot-Marie-Tooth disease, axonal, type 2z 2019-08-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 252 of the MORC2 protein (p.Arg252Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with disease in multiple families affected with Charcot-Marie-Tooth disease, type 2 (CMT2) (PMID: 26497905, 26659848). It has also been reported in sporadic cases of CMT2 (PMID: 26497905, 26912637, 27105987), two of which were reported to have arisen de novo in the affected individuals. This variant is also known as p.Arg190Trp in the literature. ClinVar contains an entry for this variant (Variation ID: 218307). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000624201 SCV000742292 pathogenic Inborn genetic diseases 2017-03-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Mendelics RCV000202547 SCV001141405 pathogenic Charcot-Marie-Tooth disease, axonal, type 2z 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091566 SCV001247691 pathogenic not provided 2017-04-01 criteria provided, single submitter clinical testing
OMIM RCV000202547 SCV000257499 pathogenic Charcot-Marie-Tooth disease, axonal, type 2z 2015-10-24 no assertion criteria provided literature only
Genesis Genome Database RCV000857122 SCV000999700 uncertain significance Charcot-Marie-Tooth disease 2019-08-14 no assertion criteria provided research
Genesis Genome Database RCV000857123 SCV000999701 uncertain significance Distal spinal muscular atrophy 2019-08-14 no assertion criteria provided research

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