Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000794765 | SCV000934193 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2022-06-18 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 641509). This variant has not been reported in the literature in individuals affected with BSCL2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 96 of the BSCL2 protein (p.Arg96Ser). |
| Victorian Clinical Genetics Services, |
RCV004789193 | SCV005400083 | uncertain significance | Neuronopathy, distal hereditary motor, type 5C | 2022-06-24 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene. Loss of function has been associated encephalopathy, progressive, with or without lipodystrophy (MIM#615924) and lipodystrophy, congenital generalized, type 2 (MIM#269700). A gain of function mechanism has been associated with neuropathy, distal hereditary motor, type VC (MIM#619112) and Silver spastic paraplegia syndrome (MIM#270685; PMID: 14981520). (I) 0108 - This gene is associated with both recessive and dominant disease. There is emerging evidence of a dominant form of epileptic encephalopathy associated with this gene (PMID: 31369919). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to serine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (v2) for a condition (2 heterozygotes, 0 homozygotes). (SP) 0309 - Multiple alternative amino acid changes at the same position have been observed in gnomAD (v2) (highest allele count: 4 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated seipin superfamily domaion (NCBI). (I) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Arg160His) has been observed in one individual with distal hereditary motor neuropathy (PMID: 26815532). Another comparable missense variant, p.(Arg160Cys), has inconclusive previous evidence for pathogenicity, having been classified as a VUS by a clinical laboratory in ClinVar. (SP) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been classified as a VUS by a clinical laboratory in ClinVar. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Athena Diagnostics | RCV004997325 | SCV005621965 | uncertain significance | not provided | 2023-12-29 | criteria provided, single submitter | clinical testing | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity. (http://gnomad.broadinstitute.org) Computational tools predict that this variant is damaging. |
| Inherited Neuropathy Consortium | RCV001027498 | SCV001190073 | likely pathogenic | Charcot-Marie-Tooth disease | no assertion criteria provided | provider interpretation | ||
| Inherited Neuropathy Consortium Ii, |
RCV003311890 | SCV004011970 | uncertain significance | Berardinelli-Seip congenital lipodystrophy | 2017-09-28 | no assertion criteria provided | literature only |