ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2951C>T (p.Pro984Leu)

gnomAD frequency: 0.00002  dbSNP: rs755143457
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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 RCV001241626 SCV001414657 uncertain significance Niemann-Pick disease, type C1 2022-07-23 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 984 of the NPC1 protein (p.Pro984Leu). This variant is present in population databases (rs755143457, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NPC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 966848). 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 not expected to disrupt NPC1 protein function. 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.
Natera, Inc. RCV001241626 SCV002095178 uncertain significance Niemann-Pick disease, type C1 2020-01-10 no assertion criteria provided clinical testing

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