Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001851638 | SCV002178599 | uncertain significance | Neuronal ceroid lipofuscinosis | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 123 of the CLN6 protein (p.Gly123Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with neuronal ceroid lipofuscinosis (PMID: 11727201; Invitae). ClinVar contains an entry for this variant (Variation ID: 4079). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CLN6 protein function. Experimental studies have shown that this missense change affects CLN6 function (PMID: 18811591, 20020536). 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. |
| Gene |
RCV002468959 | SCV002765850 | likely pathogenic | not provided | 2022-06-15 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a damaging effect as this variant leads to rapid degradation of polypeptides (Oresic et al., 2009; Kurze et al., 2010); This variant is associated with the following publications: (PMID: 19440452, 20020536, 15265688, 18811591, 12673792, 11727201) |
| Illumina Laboratory Services, |
RCV002468959 | SCV003802852 | uncertain significance | not provided | 2022-11-11 | criteria provided, single submitter | clinical testing | The CLN6 c.368G>A (p.Gly123Asp) missense variant results in the substitution of glycine at amino acid position 123 with aspartic acid. This variant has been reported in a homozygous state in one individual with neuronal ceroid lipofuscinosis (PMID: 11727201). The c.368G>A variant is reported in the Genome Aggregation Database in one allele at a frequency of 0.000065 in the Latino/Admixed American population (version 3.1.2). Functional studies have demonstrated that the c.368G>A variant protein is localized in the transmembrane domain 3 and can form dimers; however, the protein is unstable and is rapidly degraded (PMID: 20020536). Multiple lines of computational evidence suggest the variant may have a deleterious effect on the gene or gene product. Based on the available evidence, the c.368G>A (p.Gly123Asp) variant is classified as a variant of uncertain significance for neuronal ceroid lipofuscinosis. |
| Fulgent Genetics, |
RCV005007822 | SCV005630990 | likely pathogenic | Ceroid lipofuscinosis, neuronal, 6A; Ceroid lipofuscinosis, neuronal, 6B (Kufs type) | 2024-01-08 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000004294 | SCV000024460 | pathogenic | Ceroid lipofuscinosis, neuronal, 6A | 2002-02-01 | no assertion criteria provided | literature only |