ClinVar Miner

Submissions for variant NM_001136473.1(LITAF):c.334G>A (p.Gly112Ser) (rs104894519)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000006429 SCV000253888 pathogenic Charcot-Marie-Tooth disease, type 1C 2020-10-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 112 of the LITAF protein (p.Gly112Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with CMT1C in 3 independent multi-generation families, with over 20 affected, variant positive individuals and at least 4 unaffected, variant negative individuals observed (PMID: 15776429, 15122712, 12525712). ClinVar contains an entry for this variant (Variation ID: 6057). Experimental studies have shown that this missense change leads to cellular mislocalization of the LITAF protein and a reduction in the amount of exosomes and secreted exosomal proteins (PMID: 25058650, 23576546). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000235719 SCV000255673 pathogenic not provided 2018-07-26 criteria provided, single submitter clinical testing
GeneDx RCV000235719 SCV000293113 pathogenic not provided 2021-02-24 criteria provided, single submitter clinical testing Published functional studies demonstrate that G112S alters the intracellular localization of LITAF protein as well as the production of exosomes (Zhu et al., 2013; Lacerda et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20301384, 15776429, 12525712, 27549087, 28981955, 15786462, 1407588, 2239969, 23319192, 23576546, 25058650, 15122712, 24604904, 32399692, 33359733, 30373780, 31211173, 31827005, 32665875, 28211240, 32376792)
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173620 SCV001336720 pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000006429 SCV001428484 pathogenic Charcot-Marie-Tooth disease, type 1C 2019-01-14 criteria provided, single submitter clinical testing
OMIM RCV000006429 SCV000026612 pathogenic Charcot-Marie-Tooth disease, type 1C 2005-04-01 no assertion criteria provided literature only
GeneReviews RCV000006429 SCV000055877 pathologic Charcot-Marie-Tooth disease, type 1C 2012-10-18 no assertion criteria provided curation Converted during submission to Pathogenic.
Genomics England Pilot Project,Genomics England RCV000006429 SCV001760355 likely pathogenic Charcot-Marie-Tooth disease, type 1C no assertion criteria provided clinical testing

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