ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.748C>G (p.Arg250Gly) (rs950362413)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000477996 SCV000569085 uncertain significance not provided 2015-12-31 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLN6 gene. The R250G variant has notbeen 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 inthe NHLBI Exome Sequencing Project, indicating it is not a common benign variant in thesepopulations. The R250G variant is a non-conservative amino acid substitution, which is likely toimpact secondary protein structure as these residues differ in polarity, charge, size and/or otherproperties. Multiple missense variants in nearby residues have been reported in Human Gene MutationDatabase in association with late-infantile neuronal ceroid lipofuscinosis (vLINCL) (Stenson et al.,2014), supporting the functional importance of this region of the protein. However, this substitutionoccurs at a position where amino acids with similar properties to Arginine are tolerated across speciesand in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging tothe protein structure/function. Therefore, based on the currently available information, it is unclearwhether this variant is a pathogenic variant or a rare benign variant.

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