ClinVar Miner

Submissions for variant NM_004208.4(AIFM1):c.1019T>C (p.Met340Thr) (rs1057518895)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415225 SCV000492840 likely pathogenic Sensorineural hearing loss disorder; Pes planus; Distal muscle weakness; Foot dorsiflexor weakness 2015-08-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001311404 SCV001501562 pathogenic not provided 2020-12-01 criteria provided, single submitter clinical testing
Invitae RCV001385157 SCV001584918 pathogenic Charcot-Marie-Tooth Neuropathy X; Combined oxidative phosphorylation deficiency 2020-09-24 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 340 of the AIFM1 protein (p.Met340Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 25590979, 31523922, 28967629). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 374094). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AIFM1 protein function. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789722 SCV000929099 uncertain significance Cowchock syndrome no assertion criteria provided literature only
OMIM RCV000789722 SCV001052585 pathogenic Cowchock syndrome 2019-12-10 no assertion criteria provided literature only

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