Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV003475836 | SCV004200308 | likely pathogenic | Arthrogryposis multiplex congenita 6 | 2023-04-05 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003514331 | SCV004293402 | likely pathogenic | Nemaline myopathy 2 | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2431 of the NEB protein (p.Glu2431Lys). This variant is present in population databases (rs767302772, gnomAD 0.002%). This missense change has been observed in individual(s) with nemaline myopathy (PMID: 16917880, 27854218; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 242433). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on NEB function (PMID: 25110572). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689691 | SCV005185175 | uncertain significance | not specified | 2024-05-21 | criteria provided, single submitter | clinical testing | Variant summary: NEB c.7291G>A (p.Glu2431Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 248946 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.7291G>A has been reported in the literature in at least one compound heterozygous individual affected with Nemaline Myopathy 2 (Lehtokari_2006). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Marttila_2014). The following publications have been ascertained in the context of this evaluation (PMID: 16917880, 25205138, 25110572). ClinVar contains an entry for this variant (Variation ID: 242433). Based on the evidence outlined above, the variant was classified as uncertain significance. |