ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2848G>A (p.Val950Met) (rs120074135)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212760 SCV000208908 pathogenic not provided 2016-05-27 criteria provided, single submitter clinical testing The V950M variant in the NPC1 gene has been reported previously in association with Niemann-Pick disease, type C (NPC) (Millat et al., 2001; Millat et al., 2005). A patient with NPC who was homozygous for the V950M variant had adult onset of neurological symptoms (Millat et al., 2001).
Counsyl RCV000003105 SCV000221112 likely pathogenic Niemann-Pick disease type C1 2015-02-03 criteria provided, single submitter literature only
Invitae RCV000003105 SCV000770848 likely pathogenic Niemann-Pick disease type C1 2017-12-04 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 950 of the NPC1 protein (p.Val950Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Niemann-Pick disease type C (PMID: 11333381, 27900365, 26984608, 17003072). ClinVar contains an entry for this variant (Variation ID: 2971). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000003105 SCV000893487 likely pathogenic Niemann-Pick disease type C1 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000003105 SCV000023263 pathogenic Niemann-Pick disease type C1 2001-06-01 no assertion criteria provided literature only
Shendure Lab,University of Washington RCV000003105 SCV000297807 pathogenic Niemann-Pick disease type C1 2016-08-01 no assertion criteria provided clinical testing patient had late-onset NPC

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