Submissions for variant NM_006790.3(MYOT):c.1159G>A (p.Glu387Lys)

gnomAD frequency: 0.00004  dbSNP: rs373489115

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000813987	SCV000954374	uncertain significance	Myofibrillar myopathy 3	2023-12-31	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 387 of the MYOT protein (p.Glu387Lys). This variant is present in population databases (rs373489115, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of MYOT-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 657395). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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	RCV001572653	SCV001983825	uncertain significance	not provided	2021-10-13	criteria provided, single submitter	clinical testing	Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002538180	SCV003698054	uncertain significance	Inborn genetic diseases	2022-07-22	criteria provided, single submitter	clinical testing	The c.1159G>A (p.E387K) alteration is located in exon 8 (coding exon 7) of the MYOT gene. This alteration results from a G to A substitution at nucleotide position 1159, causing the glutamic acid (E) at amino acid position 387 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000813987	SCV003810975	uncertain significance	Myofibrillar myopathy 3	2021-08-17	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572653	SCV001797358	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001572653	SCV001808268	uncertain significance	not provided		no assertion criteria provided	clinical testing