ClinVar Miner

Submissions for variant NM_001363118.2(SLC52A2):c.401C>T (p.Pro134Leu)

gnomAD frequency: 0.00001  dbSNP: rs1447838904
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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 RCV000799056 SCV000938703 uncertain significance Brown-Vialetto-van Laere syndrome 2 2022-02-24 criteria provided, single submitter clinical testing 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. 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 SLC52A2 protein function. ClinVar contains an entry for this variant (Variation ID: 645041). This missense change has been observed in individual(s) with SLC52A2-related conditions (PMID: 26669662). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 134 of the SLC52A2 protein (p.Pro134Leu).
Neuberg Centre For Genomic Medicine, NCGM RCV000799056 SCV005329473 uncertain significance Brown-Vialetto-van Laere syndrome 2 2023-05-20 criteria provided, single submitter clinical testing The observed missense variant c.401C>T(p.Pro134Leu) in SLC52A2 gene has been reported previously in homozygous state in two individuals with SLC52A2-related conditions (Guissart C, et al., 2016). The c.401C>T variant has 0.001% allele frequency in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. However, study on multiple affected individuals and functional impact of the variant is not available. Multiple lines of computational evidence (Polyphen, SIFT and Mutation Taster) predict a damaging effect on protein structure and function for this variant. The amino acid Proline at position 134 is changed to a Leucine changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Pro134Leu in SLC52A2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
OMIM RCV000799056 SCV005889533 pathogenic Brown-Vialetto-van Laere syndrome 2 2025-03-17 no assertion criteria provided literature only

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