ClinVar Miner

Submissions for variant NM_018161.5(NADSYN1):c.395G>T (p.Trp132Leu)

gnomAD frequency: 0.00016  dbSNP: rs189928649
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV003405294 SCV004113117 uncertain significance NADSYN1-related disorder 2023-03-06 criteria provided, single submitter clinical testing The NADSYN1 c.395G>T variant is predicted to result in the amino acid substitution p.Trp132Leu. This variant has been reported in the compound heterozygous state in an individual with NAD deficiency (Szot et al. 2020. PubMed ID: 31883644). Functional assays in this same report showed that the p.Trp132Leu substitution causes a decrease in enzymatic activity of the protein (Szot et al. 2020. PubMed ID: 31883644). This variant is reported in 0.32% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-71175176-G-T). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx RCV004590090 SCV005079612 uncertain significance not provided 2023-12-04 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with reduced protein expression and activity (PMID: 31883644); Observed with a variant on the opposite allele (in trans) in a patient in published literature (PMID: 35491967); Observed with a variant on the opposite allele (in trans) in a fetus in published literature (PMID: 31883644); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35491967, 31883644, 36951206, 37300479)
Embryology Laboratory, Victor Chang Cardiac Research Institute RCV001078187 SCV001244273 pathogenic Congenital NAD deficiency disorder 2019-12-01 no assertion criteria provided research This variant, c.395G>T, was found in compound heterozygosity with the pathogenic variant c.145T>C

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