ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.1700A>G (p.Tyr567Cys)

gnomAD frequency: 0.00003  dbSNP: rs148726767
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000262993 SCV000338567 uncertain significance not provided 2016-01-22 criteria provided, single submitter clinical testing
Invitae RCV000702895 SCV000831769 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-10-18 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 567 of the TMEM67 protein (p.Tyr567Cys). This variant is present in population databases (rs148726767, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TMEM67-related conditions. ClinVar contains an entry for this variant (Variation ID: 285516). 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 TMEM67 protein function. 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.
CeGaT Center for Human Genetics Tuebingen RCV000262993 SCV001155457 uncertain significance not provided 2022-10-01 criteria provided, single submitter clinical testing TMEM67: PM2, PM3:Supporting
GeneDx RCV000262993 SCV003798766 uncertain significance not provided 2022-11-09 criteria provided, single submitter clinical testing Reported as heterozygous in a patient with a phenotype suggestive of autosomal recessive retinitis pigmentosa, though no second variant was identified in the TMEM67 gene (Audo et al., 2012); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22277662)
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252367 SCV001428122 uncertain significance Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

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