ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.1115G>A (p.Arg372Gln) (rs150053420)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224094 SCV000281633 uncertain significance not provided 2015-06-02 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000224094 SCV000862239 uncertain significance not provided 2018-06-29 criteria provided, single submitter clinical testing
Invitae RCV001243717 SCV001416893 uncertain significance Niemann-Pick disease type C1 2019-03-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 372 of the NPC1 protein (p.Arg372Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs150053420, ExAC 0.02%). This variant has not been reported in the literature in individuals with NPC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 235775). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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