Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000755880 | SCV000883524 | uncertain significance | not provided | 2017-11-17 | criteria provided, single submitter | clinical testing | The p.Val248Ile variant (rs754683462) has not been reported in the medical literature, is not listed in gene-specific variant databases, nor has it been previously identified in our laboratory. The p.Val248Ile variant is listed in the Genome Aggregation Database (gnomAD) browser with an overall allele frequency of 0.0032% (identified in 9 out of 277,228 chromosomes). The valine at codon 248 is highly conserved considering 12 species up to fruit fly (Alamut software v2.10.0), but computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: tolerated, PolyPhen2: benign, MutationTaster: disease causing). Based on the available information, the clinical significance of the p.Val248Ile variant cannot be determined with certainty. |
| Labcorp Genetics |
RCV001071687 | SCV001237005 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2024-04-13 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 248 of the BSCL2 protein (p.Val248Ile). This variant is present in population databases (rs754683462, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BSCL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 617998). 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) performed at Invitae indicates that this missense variant is not expected to disrupt BSCL2 protein function with a negative predictive value of 80%. 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. |
| Fulgent Genetics, |
RCV002493373 | SCV002796980 | uncertain significance | Congenital generalized lipodystrophy type 2; Hereditary spastic paraplegia 17; Severe neurodegenerative syndrome with lipodystrophy; Neuronopathy, distal hereditary motor, type 5C | 2024-03-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003166002 | SCV003869165 | uncertain significance | Inborn genetic diseases | 2023-02-23 | criteria provided, single submitter | clinical testing | The c.742G>A (p.V248I) alteration is located in exon 7 (coding exon 6) of the BSCL2 gene. This alteration results from a G to A substitution at nucleotide position 742, causing the valine (V) at amino acid position 248 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV004754555 | SCV005349942 | uncertain significance | BSCL2-related disorder | 2024-09-07 | no assertion criteria provided | clinical testing | The BSCL2 c.934G>A variant is predicted to result in the amino acid substitution p.Val312Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0096% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |