Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000317403 | SCV000331143 | benign | not specified | 2015-07-23 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000870814 | SCV001012360 | benign | Niemann-Pick disease, type C1 | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000870814 | SCV001286844 | benign | Niemann-Pick disease, type C1 | 2017-04-27 | 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Al Jalila Children’s Genomics Center, |
RCV000870814 | SCV001984544 | benign | Niemann-Pick disease, type C1 | 2020-03-24 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000317403 | SCV002103435 | benign | not specified | 2022-02-24 | criteria provided, single submitter | clinical testing | Variant summary: NPC1 c.2731G>A (p.Gly911Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00097 in 251484 control chromosomes, predominantly at a frequency of 0.011 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4.0 fold of the estimated maximal expected allele frequency for a pathogenic variant in NPC1 causing Niemann-Pick Disease Type C phenotype (0.0027), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.2731G>A in individuals affected with Niemann-Pick Disease Type C and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. |
Ce |
RCV001579491 | SCV004140859 | benign | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | NPC1: BS1, BS2 |
Breakthrough Genomics, |
RCV001579491 | SCV005251285 | benign | not provided | criteria provided, single submitter | not provided | ||
Natera, |
RCV000870814 | SCV001463702 | benign | Niemann-Pick disease, type C1 | 2020-05-04 | no assertion criteria provided | clinical testing | |
Genome Diagnostics Laboratory, |
RCV001579491 | SCV001807456 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000317403 | SCV001966690 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV001579491 | SCV002034079 | likely benign | not provided | no assertion criteria provided | clinical testing |