Submissions for variant NM_001136472.2(LITAF):c.386C>T (p.Ala129Val)

gnomAD frequency: 0.00001  dbSNP: rs201512884

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000385548	SCV000394830	uncertain significance	Charcot-Marie-Tooth disease type 1C	2018-01-12	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000385548	SCV001507877	uncertain significance	Charcot-Marie-Tooth disease type 1C	2024-05-21	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 129 of the LITAF protein (p.Ala129Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with LITAF-related conditions. ClinVar contains an entry for this variant (Variation ID: 317780). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics	RCV002356425	SCV002622407	uncertain significance	Inborn genetic diseases	2021-05-11	criteria provided, single submitter	clinical testing	The p.A129V variant (also known as c.386C>T), located in coding exon 3 of the LITAF gene, results from a C to T substitution at nucleotide position 386. The alanine at codon 129 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.