Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001002154 | SCV000457907 | likely benign | Neuronopathy, distal hereditary motor, type 2C | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Invitae | RCV001002154 | SCV000831163 | likely benign | Neuronopathy, distal hereditary motor, type 2C | 2023-10-30 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001002154 | SCV001160009 | uncertain significance | Neuronopathy, distal hereditary motor, type 2C | 2018-10-12 | criteria provided, single submitter | clinical testing | The HSPB3 c.347G>C; p.Arg116Pro variant (rs150931007) is reported in the literature in a single individual affected with myopathy and in her father, who was largely unaffected besides intermittent sciatic pain (Morelli 2017). The arginine at codon 116 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Studies of this variant in cultured cells indicate that it cannot interact with its binding partner HSPB2 and that it forms aggregates that may alter nuclear architecture. However, in the Genome Aggregation Database the p.Arg116Pro variant is found in the Ashkenazi Jewish population with an overall allele frequency of 0.39% (40/10148 alleles), which exceeds the estimated prevalence of the most common hereditary neuropathy, Charcot-Marie-Tooth disease, at 1 in 2500 (Barreto 2016). Due to conflicting information, the clinical significance of the p.Arg116Pro variant is uncertain at this time. References: Barreto LC et al. Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review. Neuroepidemiology. 2016;46(3):157-65. Morelli FF et al. Aberrant Compartment Formation by HSPB2 Mislocalizes Lamin A and Compromises Nuclear Integrity and Function. Cell Rep. 2017 Aug 29;20(9):2100-2115. |