ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2747A>G (p.Asn916Ser)

gnomAD frequency: 0.00006  dbSNP: rs756815669
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000591193 SCV000705541 uncertain significance not provided 2018-06-19 criteria provided, single submitter clinical testing
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University RCV000415351 SCV000891535 uncertain significance Niemann-Pick disease, type C1 2017-12-30 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV000415351 SCV000896683 uncertain significance Niemann-Pick disease, type C1 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000591193 SCV001788139 uncertain significance not provided 2020-11-25 criteria provided, single submitter clinical testing Reported in a patient who harbored a second NPC1 variant who also was homozygous for a variant in another gene that may have been responsible for the phenotype; phenotype information was not provided (Posey et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27959697, 27016452)
Genome-Nilou Lab RCV000415351 SCV001806024 uncertain significance Niemann-Pick disease, type C1 2021-07-14 criteria provided, single submitter clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV000415351 SCV001984556 uncertain significance Niemann-Pick disease, type C1 2020-07-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000415351 SCV003298227 uncertain significance Niemann-Pick disease, type C1 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 916 of the NPC1 protein (p.Asn916Ser). This variant is present in population databases (rs756815669, gnomAD 0.02%). This missense change has been observed in individual(s) with Niemann-Pick disease type C (PMID: 27016452). ClinVar contains an entry for this variant (Variation ID: 374343). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NPC1 protein function. 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.
Baylor Genetics RCV000415351 SCV000328825 uncertain significance Niemann-Pick disease, type C1 2015-05-06 no assertion criteria provided clinical testing Our laboratory reported dual molecular diagnoses inMTPAP (NM_018109.3, c.1468G>T) and NPC1 (NM_000271.3, c.839delT and c.2747A>G - phase unknown) in one individual with reported features of global developmental delay, developmental regression, central hypotonia, short stature, failure to thrive, familial neurodegenerative disease, cerebellar problems on brain MRI, absence like episodes, left hip dislocation, and constipation.
Natera, Inc. RCV000415351 SCV002095185 uncertain significance Niemann-Pick disease, type C1 2020-02-17 no assertion criteria provided clinical testing

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