ClinVar Miner

Submissions for variant NM_006790.2(MYOT):c.1401T>A (p.Asn467Lys) (rs145427063)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000313284 SCV000453022 uncertain significance Spheroid body myopathy 2018-01-13 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.
Illumina Clinical Services Laboratory,Illumina RCV000367931 SCV000453023 uncertain significance Limb-Girdle Muscular Dystrophy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000391315 SCV000453024 uncertain significance Myofibrillar Myopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487879 SCV000575441 uncertain significance not provided 2016-12-01 criteria provided, single submitter clinical testing
GeneDx RCV000487879 SCV000589346 uncertain significance not provided 2017-06-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYOT gene. The N467K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N467K variant is observed in 1/6,614 (0.015%) alleles from individuals of Finnish background in large population cohorts (Lek et al., 2016). The N467K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, 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 RCV000529217 SCV000638808 uncertain significance Myofibrillar myopathy 3 2020-11-02 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 467 of the MYOT protein (p.Asn467Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs145427063, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with a MYOT-related disease. ClinVar contains an entry for this variant (Variation ID: 351029). 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: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, this variant has uncertain impact on MYOT function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000487879 SCV000707808 uncertain significance not provided 2017-04-14 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765814 SCV000897204 uncertain significance Spheroid body myopathy; Myofibrillar myopathy 3 2018-10-31 criteria provided, single submitter clinical testing

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