ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2072C>T (p.Pro691Leu)

dbSNP: rs1555634422
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668135 SCV000792686 likely pathogenic Niemann-Pick disease, type C1 2017-07-07 criteria provided, single submitter clinical testing
Invitae RCV000668135 SCV001586304 pathogenic Niemann-Pick disease, type C1 2021-06-22 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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"). This variant has been observed in individuals with Niemann-Pick disease type C (PMID: 25236789, 12955717, 27139891, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 552803). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 691 of the NPC1 protein (p.Pro691Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine.
GeneDx RCV003128721 SCV003805395 likely pathogenic not provided 2023-02-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25236789, 27139891, 32248828, 12955717, 27535533, 33624863)

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