ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.21769T>A (p.Ser7257Thr) (rs191722579)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486783 SCV000574108 uncertain significance not provided 2017-03-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NEB gene. The S7257T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S7257T variant is observed in 17/66684 (0.03%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved in mammals. However, the S7257T variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000537873 SCV000640690 uncertain significance Nemaline myopathy 2 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 7257 of the NEB protein (p.Ser7257Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine. This variant is present in population databases (rs191722579, ExAC 0.03%). This variant has not been reported in the literature in individuals with an NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 424311). 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: Not Available; 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.
Natera, Inc. RCV000537873 SCV001460595 uncertain significance Nemaline myopathy 2 2020-01-17 no assertion criteria provided 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.