Submissions for variant NM_000252.3(MTM1):c.1469A>G (p.Lys490Arg)

dbSNP: rs781948606

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001529349	SCV002001720	uncertain significance	not provided	2021-04-09	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568163	SCV003447935	uncertain significance	Severe X-linked myotubular myopathy	2022-08-30	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 490 of the MTM1 protein (p.Lys490Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MTM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1174940). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Ambry Genetics	RCV003365426	SCV004071330	uncertain significance	Inborn genetic diseases	2023-06-26	criteria provided, single submitter	clinical testing	The c.1469A>G (p.K490R) alteration is located in exon 14 (coding exon 13) of the MTM1 gene. This alteration results from a A to G substitution at nucleotide position 1469, causing the lysine (K) at amino acid position 490 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529349	SCV001742631	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529349	SCV001973306	uncertain significance	not provided		no assertion criteria provided	clinical testing