ClinVar Miner

Submissions for variant NM_001062.4(TCN1):c.980C>G (p.Pro327Arg)

gnomAD frequency: 0.00026  dbSNP: rs36044892
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756751 SCV000884657 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing The p.Pro327Arg variant (rs36044892) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.01 percent (identified on 29 out of 276,890 chromosomes). The proline at position 327 is moderately conserved considering ten species (Alamut v2.9.0) and computational analyses of the effects of the variant on protein structure and function indicates conflicting results (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Pro327Arg variant with certainty.
Labcorp Genetics (formerly Invitae), Labcorp RCV001869025 SCV002176293 uncertain significance Transcobalamin I deficiency 2022-08-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 327 of the TCN1 protein (p.Pro327Arg). This variant is present in population databases (rs36044892, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TCN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 618415). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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