ClinVar Miner

Submissions for variant NM_001044385.3(TMEM237):c.330T>G (p.Asn110Lys) (rs1553660992)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519206 SCV000619840 uncertain significance not provided 2018-12-19 criteria provided, single submitter clinical testing The N110K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N110K variant is not observed in large population cohorts (Lek et al., 2016). The N110K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001345807 SCV001539946 uncertain significance Joubert syndrome 14 2020-10-07 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 110 of the TMEM237 protein (p.Asn110Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TMEM237-related conditions. ClinVar contains an entry for this variant (Variation ID: 451176). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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