ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2973_2974delinsAT (p.Gly992Trp)

dbSNP: rs1555632971
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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 RCV000649019 SCV000770840 likely pathogenic Niemann-Pick disease, type C1 2020-01-11 criteria provided, single submitter clinical testing 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different variant (c.2974G>T) giving rise to the same protein effect observed here (p.Gly992Trp) has been reported to be a very common cause of Niemann-Pick disease type C (PMID: 9634529, 12955717), indicating that this residue may be critical for protein function. This variant has not been reported in the literature in individuals with NPC1-related disease. This variant is not present in population databases (ExAC no frequency). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").
Eurofins Ntd Llc (ga) RCV000728621 SCV000856218 pathogenic not provided 2017-08-10 criteria provided, single submitter clinical testing

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