ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.194C>T (p.Pro65Leu) (rs375909006)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000214047 SCV000272196 uncertain significance not specified 2016-03-03 criteria provided, single submitter clinical testing The p.Pro65Leu variant in NEB has not been previously reported in individuals wi th myopathy, but has been identified in 12/66624 European chromosomes by the Exo me Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3759090 06). Computational prediction tools and conservation analysis do not provide str ong support for or against an impact to the protein. In summary, the clinical si gnificance of the p.Pro65Leu is uncertain.
Illumina Clinical Services Laboratory,Illumina RCV000558344 SCV000417057 uncertain significance Nemaline myopathy 2 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000558344 SCV000640643 uncertain significance Nemaline myopathy 2 2019-01-31 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 65 of the NEB protein (p.Pro65Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs375909006, ExAC 0.02%). This variant has not been reported in the literature in individuals with NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 229041). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV000214047 SCV000729286 likely benign not specified 2018-02-28 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl RCV000558344 SCV000788731 uncertain significance Nemaline myopathy 2 2017-01-06 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.