ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.679G>C (p.Ala227Pro)

gnomAD frequency: 0.00001  dbSNP: rs767886819
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001334628 SCV001527526 uncertain significance COACH syndrome 1 2018-08-22 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV001865813 SCV002243524 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2021-08-25 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 227 of the TMEM67 protein (p.Ala227Pro). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and proline. This variant is present in population databases (rs767886819, ExAC 0.009%). 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: 1032510). 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 not 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.
Fulgent Genetics, Fulgent Genetics RCV002499658 SCV002793309 uncertain significance COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 2021-11-12 criteria provided, single submitter clinical testing

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