ClinVar Miner

Submissions for variant NM_213720.3(CHCHD10):c.196G>A (p.Gly66Ser)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812293 SCV000952602 uncertain significance Spinal muscular atrophy, jokela type; Frontotemporal dementia and/or amyotrophic lateral sclerosis 2; Myopathy, isolated mitochondrial, autosomal dominant 2018-11-14 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 66 of the CHCHD10 protein (p.Gly66Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs374211312, ExAC 0.005%). This variant has been observed in an individual affected with amyotrophic lateral sclerosis (PMID: 25700176). Experimental studies have shown that this missense change leads to intra-mitochondrial clustering in vitro (PMID: 29789341). This variant disrupts the p.Gly66 amino acid residue in CHCHD10. Other variant(s) that disrupt this residue have been observed in individuals affected with spinal motor neuropathy, Jokela-type  (SMAJ) (PMID: 22535186, 25428574, 26224640, 27810918, 29315381), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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.

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