ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.41G>A (p.Gly14Asp)

gnomAD frequency: 0.00011  dbSNP: rs994590268
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000703145 SCV000832030 uncertain significance Neuronal ceroid lipofuscinosis 2022-09-30 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 14 of the CLN6 protein (p.Gly14Asp). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CLN6-related conditions. ClinVar contains an entry for this variant (Variation ID: 579778). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CLN6 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.
Fulgent Genetics, Fulgent Genetics RCV000763980 SCV000894931 uncertain significance Ceroid lipofuscinosis, neuronal, 6A; Adult neuronal ceroid lipofuscinosis 2018-10-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000703145 SCV001278034 uncertain significance Neuronal ceroid lipofuscinosis 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.
GeneDx RCV001566395 SCV001789905 uncertain significance not provided 2020-03-06 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function Has not been previously published as pathogenic or benign to our knowledge Observed in 0.0116% (13/112448 alleles) in large population cohorts (Lek et al., 2016)

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