Submissions for variant NM_006790.3(MYOT):c.1203T>A (p.Asp401Glu)

gnomAD frequency: 0.00006  dbSNP: rs78633961

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723809	SCV000203056	uncertain significance	not provided	2016-12-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001437646	SCV000453013	likely benign	Myofibrillar myopathy 3	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000323304	SCV000453014	uncertain significance	Myofibrillar Myopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000378013	SCV000453015	uncertain significance	Limb-Girdle Muscular Dystrophy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000723809	SCV000619653	uncertain significance	not provided	2017-08-01	criteria provided, single submitter	clinical testing	The D401E variant in the MYOT gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D401E variant is observed in 15/8192 (0.2%) alleles from individuals of East Asian background, in the ExAC dataset (Lek et al., 2016). The D401E variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret D401E as a variant of uncertain significance
Labcorp Genetics (formerly Invitae), Labcorp	RCV001437646	SCV001640505	likely benign	Myofibrillar myopathy 3	2025-01-28	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001437646	SCV003817874	uncertain significance	Myofibrillar myopathy 3	2023-05-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004019839	SCV004955550	uncertain significance	Inborn genetic diseases	2024-01-23	criteria provided, single submitter	clinical testing	The c.1203T>A (p.D401E) alteration is located in exon 9 (coding exon 8) of the MYOT gene. This alteration results from a T to A substitution at nucleotide position 1203, causing the aspartic acid (D) at amino acid position 401 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.