Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001385145 | SCV001584903 | pathogenic | Neuronal ceroid lipofuscinosis | 2023-06-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1072428). For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This missense change has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 21549341, 30561534). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces phenylalanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 238 of the CLN6 protein (p.Phe238Thr). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001385145 | SCV004099528 | pathogenic | Neuronal ceroid lipofuscinosis | 2023-09-05 | criteria provided, single submitter | clinical testing | Variant summary: CLN6 c.712_713delinsAC (p.Phe238Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250998 control chromosomes. c.712_713delinsAC has been reported in the literature in multiple individuals affected with adult onset Neuronal Ceroid-Lipofuscinosis (Kufs disease) (Berkovic_2019, Arsov_2011). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21549341, 30561534). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |