ClinVar Miner

Submissions for variant NM_001905.4(CTPS1):c.472C>T (p.Pro158Ser)

gnomAD frequency: 0.00008  dbSNP: rs140029453
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000804430 SCV000944341 uncertain significance Severe combined immunodeficiency due to CTPS1 deficiency 2022-10-03 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 158 of the CTPS1 protein (p.Pro158Ser). This variant is present in population databases (rs140029453, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CTPS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 649485). 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: "Possibly 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.
Genetic Services Laboratory, University of Chicago RCV001816869 SCV002065768 uncertain significance not specified 2021-12-08 criteria provided, single submitter clinical testing DNA sequence analysis of the CTPS1 gene demonstrated a sequence change, c.472C>T, in exon 5 that results in an amino acid change, p.Pro158Ser. This sequence change has been described in the gnomAD database with a frequency of 0.009% in the non-Finnish European subpopulation (dbSNP rs140029453). The p.Pro158Ser change affects a highly conserved amino acid residue located in a domain of the CTPS1 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Pro158Ser substitution. This sequence change does not appear to have been previously described in individuals with CTPS1-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Pro158Ser change remains unknown at this time.

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