Submissions for variant NM_001136473.1(LITAF):c.*117C>T (rs748017885)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236601	SCV000292598	uncertain significance	not provided	2015-08-10	criteria provided, single submitter	clinical testing	The R160C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. 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 R160C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173621	SCV001336722	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Invitae	RCV001218448	SCV001390330	uncertain significance	Charcot-Marie-Tooth disease, type 1C	2019-06-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with cysteine at codon 160 of the LITAF protein (p.Arg160Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs748017885, ExAC 0.002%). This variant has been observed in individuals affected with Charcot-Marie-Tooth disease and to segregate with disease in families (PMID: 28211240). ClinVar contains an entry for this variant (Variation ID: 245638). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; 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.

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