ClinVar Miner

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

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Total submissions: 7
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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 pathogenic Niemann-Pick disease type C1 2020-10-06 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 observed in individual(s) with Niemann-Pick disease type C (PMID: 11333381, 27900365, 26984608, 17003072). ClinVar contains an entry for this variant (Variation ID: 2971). This variant has been reported to have conflicting or insufficient data to determine the effect on NPC1 protein function (PMID: 30923329, 31699992, 28193631). This variant disrupts the p.Val950 amino acid residue in NPC1. Other variant(s) that disrupt this residue have been observed in individuals with NPC1-related conditions (PMID: 26981555, 25236789), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000003105 SCV000893487 likely pathogenic Niemann-Pick disease type C1 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000003105 SCV001528305 pathogenic Niemann-Pick disease type C1 2018-03-14 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. The c.2848G>A (p.V950M) variant has been previously reported in multiple patients with adult-onset Niemann-Pick disease and variant biochemical phenotype [PMID 11333381, 16126423, 26984608, 27900365]
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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