ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3020C>T (p.Pro1007Leu)

dbSNP: rs764789542
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centogene AG - the Rare Disease Company RCV001250198 SCV001424467 pathogenic Niemann-Pick disease, type C1 criteria provided, single submitter clinical testing
Invitae RCV001250198 SCV003442628 pathogenic Niemann-Pick disease, type C1 2023-05-15 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1007 of the NPC1 protein (p.Pro1007Leu). This variant is present in population databases (rs764789542, gnomAD 0.003%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro1007 amino acid residue in NPC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10521290, 11754101, 14639697, 15937921, 23183285, 25425405). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 NPC1 protein function. ClinVar contains an entry for this variant (Variation ID: 973559). This missense change has been observed in individuals with Niemann-Pick type C (PMID: 26666848).

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