ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.1115C>A (p.Thr372Lys)

gnomAD frequency: 0.00001  dbSNP: rs863225235
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program, University of Washington RCV000201528 SCV000256520 pathogenic Joubert syndrome 6 2015-02-23 criteria provided, single submitter research
GeneDx RCV000419395 SCV000521232 likely pathogenic not provided 2022-06-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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: 19574260, 26092869, 19058225, 20232449, 19466712, 28838911, 32000717)
Invitae RCV000636949 SCV000758397 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2023-09-28 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 372 of the TMEM67 protein (p.Thr372Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with Joubert syndrome (PMID: 12368986, 19058225, 19574260, 20232449, 25920555, 26092869). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217726). 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. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002478718 SCV000894454 pathogenic COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 2021-10-29 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000419395 SCV003814115 likely pathogenic not provided 2022-06-29 criteria provided, single submitter clinical testing

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