Submissions for variant NM_001042432.2(CLN3):c.270T>G (p.Phe90Leu)

dbSNP: rs145520962

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000178825	SCV000230987	uncertain significance	not provided	2014-05-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000632679	SCV000753865	uncertain significance	Neuronal ceroid lipofuscinosis	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 90 of the CLN3 protein (p.Phe90Leu). This variant is present in population databases (rs145520962, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CLN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 197710). 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: "Possibly Damaging"; 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.
Fulgent Genetics, Fulgent Genetics	RCV000765283	SCV000896536	uncertain significance	Neuronal ceroid lipofuscinosis 3	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000765283	SCV001279574	uncertain significance	Neuronal ceroid lipofuscinosis 3	2018-01-15	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.
GeneDx	RCV000178825	SCV001811053	uncertain significance	not provided	2020-03-03	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Genome-Nilou Lab	RCV000765283	SCV002027132	uncertain significance	Neuronal ceroid lipofuscinosis 3	2021-09-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426857	SCV002743535	uncertain significance	Inborn genetic diseases	2022-01-13	criteria provided, single submitter	clinical testing	The c.270T>G (p.F90L) alteration is located in exon 5 (coding exon 4) of the CLN3 gene. This alteration results from a T to G substitution at nucleotide position 270, causing the phenylalanine (F) at amino acid position 90 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004816294	SCV005072575	uncertain significance	Retinal dystrophy	2020-01-01	no assertion criteria provided	clinical testing