ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.2932G>A (p.Val978Ile)

gnomAD frequency: 0.00004  dbSNP: rs371965185
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001867481 SCV002136079 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 978 of the TMEM67 protein (p.Val978Ile). This variant is present in population databases (rs371965185, gnomAD 0.01%). 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: 1368396). 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.
Ambry Genetics RCV004040442 SCV004967283 uncertain significance Inborn genetic diseases 2023-12-18 criteria provided, single submitter clinical testing The c.2932G>A (p.V978I) alteration is located in exon 28 (coding exon 28) of the TMEM67 gene. This alteration results from a G to A substitution at nucleotide position 2932, causing the valine (V) at amino acid position 978 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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