ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.2323A>G (p.Ile775Val)

gnomAD frequency: 0.00008  dbSNP: rs200145042
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001937721 SCV002182025 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 775 of the TMEM67 protein (p.Ile775Val). This variant is present in population databases (rs200145042, gnomAD 0.02%). 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: 1407135). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
GeneDx RCV002282644 SCV002571229 uncertain significance not provided 2022-03-08 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002490238 SCV002781143 uncertain significance COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002555684 SCV003534818 uncertain significance Inborn genetic diseases 2022-11-30 criteria provided, single submitter clinical testing The c.2323A>G (p.I775V) alteration is located in exon 23 (coding exon 23) of the TMEM67 gene. This alteration results from a A to G substitution at nucleotide position 2323, causing the isoleucine (I) at amino acid position 775 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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