ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.100G>A (p.Ala34Thr) (rs146198681)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187079 SCV000240654 likely benign not specified 2015-01-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000727122 SCV000705940 uncertain significance not provided 2017-08-25 criteria provided, single submitter clinical testing
Invitae RCV000632687 SCV000753873 uncertain significance Neuronal ceroid lipofuscinosis 2019-10-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 34 of the CLN6 protein (p.Ala34Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs146198681, ExAC 0.04%). This variant has been reported as heterozygous in an individual affected with Kufs disease type B (adult neuronal ceroid lipofuscinosis) (PMID: 21549341). ClinVar contains an entry for this variant (Variation ID: 205152). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV000632687 SCV001276321 uncertain significance Neuronal ceroid lipofuscinosis 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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