Submissions for variant NM_006790.3(MYOT):c.179C>G (p.Ser60Cys)

dbSNP: rs121908458

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725007	SCV000333146	pathogenic	not provided	2017-10-13	criteria provided, single submitter	clinical testing
Invitae	RCV000006193	SCV000638812	pathogenic	Myofibrillar myopathy 3	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 60 of the MYOT protein (p.Ser60Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with myofibrillar myopathy (PMID: 15111675, 16684602, 19225410, 21676617, 22349301, 26842778). ClinVar contains an entry for this variant (Variation ID: 5836). 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. Experimental studies have shown that this missense change affects MYOT function (PMID: 21361873, 22349301). This variant disrupts the p.Ser60 amino acid residue in MYOT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16684602, 16793270, 19590214, 26842778). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV000725007	SCV001714143	pathogenic	not provided	2020-07-08	criteria provided, single submitter	clinical testing	PS3, PS4_moderate, PM2, PP4, PP5
GeneDx	RCV000725007	SCV001812081	pathogenic	not provided	2022-03-22	criteria provided, single submitter	clinical testing	Published functional studies demonstrate reduced degradation of myotilin (von Nandelstadh et al., 2011); Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22349301, 15947064, 21676617, 15111675, 27618136, 21361873, 32403337, 32041727)
Revvity Omics, Revvity	RCV000006193	SCV002017711	pathogenic	Myofibrillar myopathy 3	2023-12-28	criteria provided, single submitter	clinical testing
Centogene AG - the Rare Disease Company	RCV000006193	SCV002059614	pathogenic	Myofibrillar myopathy 3	2020-09-21	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000725007	SCV002770883	pathogenic	not provided	2017-09-07	criteria provided, single submitter	clinical testing	This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant affected protein organization in muscle cells (PMID: 22349301).
Fulgent Genetics, Fulgent Genetics	RCV000006193	SCV002811520	pathogenic	Myofibrillar myopathy 3	2021-09-18	criteria provided, single submitter	clinical testing
OMIM	RCV000006193	SCV000026375	pathogenic	Myofibrillar myopathy 3	2004-04-27	no assertion criteria provided	literature only
Wellcome Centre for Mitochondrial Research, Newcastle University	RCV000239643	SCV000298021	pathogenic	Myofibrillar myopathy	2016-08-16	no assertion criteria provided	clinical testing