ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.991A>C (p.Lys331Gln)

gnomAD frequency: 0.00004  dbSNP: rs769351856
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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 RCV001915157 SCV002175273 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 331 of the TMEM67 protein (p.Lys331Gln). This variant is present in population databases (rs769351856, gnomAD 0.008%). 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: 1398637). 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 RCV002482763 SCV002789333 uncertain significance COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 2021-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV004681301 SCV005176617 uncertain significance Inborn genetic diseases 2024-05-23 criteria provided, single submitter clinical testing The c.991A>C (p.K331Q) alteration is located in exon 10 (coding exon 10) of the TMEM67 gene. This alteration results from a A to C substitution at nucleotide position 991, causing the lysine (K) at amino acid position 331 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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