ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.2162C>G (p.Pro721Arg)

gnomAD frequency: 0.00007  dbSNP: rs757105976
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001923738 SCV002194716 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2024-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 721 of the TMEM67 protein (p.Pro721Arg). This variant is present in population databases (rs757105976, gnomAD 0.05%). 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: 1421324). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV002479435 SCV002777523 uncertain significance COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 2021-09-20 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004733419 SCV005354012 uncertain significance TMEM67-related disorder 2024-08-26 no assertion criteria provided clinical testing The TMEM67 c.2162C>G variant is predicted to result in the amino acid substitution p.Pro721Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.049% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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