ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.119C>T (p.Thr40Met)

dbSNP: rs769199442
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414428 SCV000491774 uncertain significance not specified 2016-11-10 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLN6 gene. The T40M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T40M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000801841 SCV000941639 uncertain significance Neuronal ceroid lipofuscinosis 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 40 of the CLN6 protein (p.Thr40Met). This variant is present in population databases (rs769199442, 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: 373196). 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 not expected to disrupt CLN6 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV002523939 SCV003738768 uncertain significance Inborn genetic diseases 2022-05-06 criteria provided, single submitter clinical testing The c.119C>T (p.T40M) alteration is located in exon 2 (coding exon 2) of the CLN6 gene. This alteration results from a C to T substitution at nucleotide position 119, causing the threonine (T) at amino acid position 40 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003144248 SCV003832409 uncertain significance not provided 2021-10-13 criteria provided, single submitter clinical testing

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