Submissions for variant NM_003383.5(VLDLR):c.732C>G (p.Ile244Met)

gnomAD frequency: 0.00026  dbSNP: rs145995735

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194738	SCV000249387	uncertain significance	not specified	2015-02-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000379212	SCV000479341	uncertain significance	Congenital cerebellar hypoplasia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001165827	SCV001328073	uncertain significance	Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001575970	SCV001803067	likely benign	not provided	2021-03-05	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 33111339)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001575970	SCV002478230	likely benign	not provided	2024-09-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002517150	SCV003687883	uncertain significance	Inborn genetic diseases	2022-05-09	criteria provided, single submitter	clinical testing	The c.732C>G (p.I244M) alteration is located in exon 5 (coding exon 5) of the VLDLR gene. This alteration results from a C to G substitution at nucleotide position 732, causing the isoleucine (I) at amino acid position 244 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect - Brain Gene Registry	RCV001165827	SCV004804540	not provided	Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1		no assertion provided	phenotyping only	Variant classified as Uncertain significance and reported on 12-06-2012 by Baylor College of Medicine. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.