ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.755G>A (p.Arg252His) (rs374681194)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187105 SCV000240680 uncertain significance not provided 2018-05-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLN6 gene. The R252H variant has been previously reported as a variant in two patients with suspected neuronal ceroid lipofuscinosis (NCL) (Kousi et al., 2012). The first patient also had a frameshift variant in CLN6; however, it was not determined if the two changes were in cis or trans, and functional/EM studies were not performed. In the second patient, a second variant was not clearly identified; however, the patient's EM studies were consistent with the diagnosis of NCL (Kousi et al., 2012). The R252H variant is observed in 14/87,770 (0.3%) alleles from individuals of Ashkenazi Jewish backgound in large population cohorts (Lek et al., 2016). The R252H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Counsyl RCV000671648 SCV000796641 uncertain significance Neuronal ceroid lipofuscinosis 6 2017-12-20 criteria provided, single submitter clinical testing
Invitae RCV001083020 SCV001003471 likely benign Neuronal ceroid lipofuscinosis 2019-12-31 criteria provided, single submitter clinical testing
Translational Research Program on Neuronal Ceroid Lipofuscinosis,Center for the Study of Inborn Errors of Metabolism RCV000671648 SCV000804310 pathogenic Neuronal ceroid lipofuscinosis 6 no assertion criteria provided research Late Infantile NCL

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