Submissions for variant NM_020949.3(SLC7A14):c.1168G>C (p.Val390Leu)

dbSNP: rs142416793

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001050504	SCV001214617	uncertain significance	not provided	2025-01-01	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 390 of the SLC7A14 protein (p.Val390Leu). This variant is present in population databases (rs142416793, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SLC7A14-related conditions. ClinVar contains an entry for this variant (Variation ID: 847045). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002307665	SCV002600314	uncertain significance	not specified	2022-10-05	criteria provided, single submitter	clinical testing	Variant summary: SLC7A14 c.1168G>C (p.Val390Leu) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00088 in 248694 control chromosomes, predominantly at a frequency of 0.0016 within the Non-Finnish European subpopulation in the gnomAD database. The variant, c.1168G>C, has been reported in the literature in heterozygous state in an individual affected with nonsyndromic retinal dystrophy (Rodriguez-Munoz_2020), however, in this patient a co-occurrence with a homozygous pathogenic variant has also been reported (RPE65 c.1022T>C, p.Leu341Ser) which could explain the patient's phenotype, therefore providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Fulgent Genetics, Fulgent Genetics	RCV002481959	SCV002788277	uncertain significance	Retinitis pigmentosa 68	2022-02-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002307665	SCV003726077	uncertain significance	not specified	2023-11-15	criteria provided, single submitter	clinical testing	The c.1168G>C (p.V390L) alteration is located in exon 7 (coding exon 6) of the SLC7A14 gene. This alteration results from a G to C substitution at nucleotide position 1168, causing the valine (V) at amino acid position 390 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV001050504	SCV005093691	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	SLC7A14: PP3, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV001050504	SCV005189887	uncertain significance	not provided		criteria provided, single submitter	not provided
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004813618	SCV005069558	uncertain significance	Optic atrophy	2023-01-01	no assertion criteria provided	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004813617	SCV005073457	uncertain significance	Retinal dystrophy	2023-01-01	no assertion criteria provided	clinical testing