Submissions for variant NM_001371596.2(MFSD8):c.1205C>T (p.Ser402Leu)

gnomAD frequency: 0.00010  dbSNP: rs200745039

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000402254	SCV000447468	uncertain significance	Neuronal ceroid lipofuscinosis 7	2018-01-13	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.
Ambry Genetics	RCV002314069	SCV000847738	uncertain significance	Inborn genetic diseases	2021-02-23	criteria provided, single submitter	clinical testing	The c.1205C>T (p.S402L) alteration is located in exon 12 (coding exon 11) of the MFSD8 gene. This alteration results from a C to T substitution at nucleotide position 1205, causing the serine (S) at amino acid position 402 to be replaced by a leucine (L). The p.S402L alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Eurofins Ntd Llc (ga)	RCV000727610	SCV000854868	uncertain significance	not provided	2018-06-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000402254	SCV001408675	uncertain significance	Neuronal ceroid lipofuscinosis 7	2022-08-16	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 402 of the MFSD8 protein (p.Ser402Leu). This variant is present in population databases (rs200745039, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MFSD8-related conditions. ClinVar contains an entry for this variant (Variation ID: 347541). 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 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.
Natera, Inc.	RCV001276176	SCV001462030	uncertain significance	Late-infantile neuronal ceroid lipofuscinosis	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000727610	SCV001923526	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000727610	SCV001963538	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000727610	SCV001968085	uncertain significance	not provided		no assertion criteria provided	clinical testing