ClinVar Miner

Submissions for variant NM_006790.2(MYOT):c.179C>G (p.Ser60Cys) (rs121908458)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725007 SCV000333146 pathogenic not provided 2017-10-13 criteria provided, single submitter clinical testing
Invitae RCV000006193 SCV000638812 pathogenic Myofibrillar myopathy 3 2020-09-24 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 60 of the MYOT protein (p.Ser60Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (rs121908458, ExAC no frequency). This variant has been reported in several individuals and families affected with myofibrillar myopathy (MFM) and is considered one of the most common causative mutations for myotilinopathy (PMID: 22349301, 15111675, 21676617, 19225410, 16684602, 26842778). ClinVar contains an entry for this variant (Variation ID: 5836). Experimental studies have shown that this missense change altered MYOT protein properties in electroporated mouse muscle and lead to protein accumulation in transfected cells (PMID: 22349301, 21361873). A different missense substitution at this codon (p.Ser60Phe) has been determined to be pathogenic (PMID: 19590214, 16793270, 16684602, 26842778). This suggests that the serine residue is critical for MYOT protein function. 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
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

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