ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3343G>T (p.Val1115Phe) (rs34226296)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000078481 SCV000110337 benign not specified 2013-02-22 criteria provided, single submitter clinical testing
GeneDx RCV000767035 SCV000492076 uncertain significance not provided 2016-12-09 criteria provided, single submitter clinical testing The V1115F variant in the NPC1 gene has been reported previously in the heterozygous state along with another heterozygous variant (S1178G), phase unknown, in a 6 year-old male with Niemann-Pick disease type C (Rodríguez-Quiroga et al., 2015). The NHLBI ESP Exome Sequencing Project reports V1115F was observed in 34/4406 alleles (0.77%) from individuals of African-American ancestry, including one homozygous individual, indicating it may be a rare benign variant in this population. The V1115F variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In addition, this substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret V1115F as a variant of uncertain significance.
Counsyl RCV000674624 SCV000799993 uncertain significance Niemann-Pick disease type C1 2018-05-16 criteria provided, single submitter clinical testing
Invitae RCV000674624 SCV001005724 benign Niemann-Pick disease type C1 2020-12-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000674624 SCV001283366 benign Niemann-Pick disease type C1 2017-10-17 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000767035 SCV001807285 uncertain significance not provided no assertion criteria provided clinical testing

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