Submissions for variant NM_006790.3(MYOT):c.532C>T (p.Arg178Cys)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002912521	SCV003246726	uncertain significance	Myofibrillar myopathy 3	2022-04-07	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 178 of the MYOT protein (p.Arg178Cys). This variant is present in population databases (rs764677626, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MYOT-related conditions. 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 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.
Ambry Genetics	RCV002912522	SCV003614328	uncertain significance	Inborn genetic diseases	2022-04-07	criteria provided, single submitter	clinical testing	The c.532C>T (p.R178C) alteration is located in exon 4 (coding exon 3) of the MYOT gene. This alteration results from a C to T substitution at nucleotide position 532, causing the arginine (R) at amino acid position 178 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526946	SCV005039300	uncertain significance	not specified	2024-03-21	criteria provided, single submitter	clinical testing	Variant summary: Variant summary: The SLC26A2 c.532C>T (p.Arg178X) variant results in a premature termination codon, predicted to cause a truncated or absent SLC26A2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.1724delA). One in silico tool predicts a damaging outcome for this variant, which has been confirmed by at least one functional study (Karniski_2004). This variant was found in 13/120994 control chromosomes at a frequency of 0.0001074, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC26A2 variant (0.002958). This variant has been reported in multiple STRO patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.