ClinVar Miner

Submissions for variant NM_017866.6(TMEM70):c.214C>T (p.Pro72Ser)

gnomAD frequency: 0.00004  dbSNP: rs143292919
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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 RCV000544415 SCV000650872 uncertain significance Mitochondrial complex V (ATP synthase) deficiency nuclear type 2 2023-08-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 72 of the TMEM70 protein (p.Pro72Ser). This variant is present in population databases (rs143292919, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TMEM70-related conditions. ClinVar contains an entry for this variant (Variation ID: 471955). 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 TMEM70 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.
Ambry Genetics RCV003362843 SCV004055454 uncertain significance Inborn genetic diseases 2023-07-26 criteria provided, single submitter clinical testing The c.214C>T (p.P72S) alteration is located in exon 2 (coding exon 2) of the TMEM70 gene. This alteration results from a C to T substitution at nucleotide position 214, causing the proline (P) at amino acid position 72 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genomics Laboratory, Stanford Medicine RCV000544415 SCV004704600 uncertain significance Mitochondrial complex V (ATP synthase) deficiency nuclear type 2 2021-04-16 criteria provided, single submitter clinical testing The p.Pro72Ser variant in the TMEM70 gene has not been previously reported in association with disease. This variant has been identified in 2/129,092 European chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Computational tools predict that the p.Pro72Ser variant does not impact protein function; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Pro72Ser variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2; BP4]

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