ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.4198G>A (p.Ala1400Thr) (rs113174390)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000210578 SCV000263026 likely benign Inborn genetic diseases 2013-12-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000309322 SCV000343560 uncertain significance not provided 2016-08-23 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000534346 SCV000417003 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 RCV000534346 SCV000640793 uncertain significance Nemaline myopathy 2 2019-10-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1400 of the NEB protein (p.Ala1400Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs113174390, ExAC 0.1%). 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: 225110). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on NEB function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV000534346 SCV001462199 likely benign Nemaline myopathy 2 2019-11-11 no assertion criteria provided clinical testing

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