ClinVar Miner

Submissions for variant NM_033109.5(PNPT1):c.1121T>C (p.Val374Ala)

gnomAD frequency: 0.00003  dbSNP: rs377657203
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001332752 SCV001525159 uncertain significance Combined oxidative phosphorylation defect type 13 2019-10-07 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001865768 SCV002308020 uncertain significance not provided 2022-08-31 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 374 of the PNPT1 protein (p.Val374Ala). This variant is present in population databases (rs377657203, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PNPT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1031030). 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 expected to disrupt PNPT1 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 RCV003263970 SCV003981842 uncertain significance Inborn genetic diseases 2023-05-17 criteria provided, single submitter clinical testing The c.1121T>C (p.V374A) alteration is located in exon 13 (coding exon 13) of the PNPT1 gene. This alteration results from a T to C substitution at nucleotide position 1121, causing the valine (V) at amino acid position 374 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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