Submissions for variant NM_000875.5(IGF1R):c.3187-5C>T

gnomAD frequency: 0.00052  dbSNP: rs45495500

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000594025	SCV000708520	uncertain significance	not provided	2017-05-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000594025	SCV001040688	benign	not provided	2024-01-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001121011	SCV001279544	uncertain significance	Growth delay due to insulin-like growth factor I resistance	2017-07-16	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001796755	SCV004122498	uncertain significance	not specified	2023-10-04	criteria provided, single submitter	clinical testing	Variant summary: IGF1R c.3187-5C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0009 in 156356 control chromosomes. To our knowledge, no occurrence of c.3187-5C>T in individuals affected with Growth Delay Due To Insulin-Like Growth Factor I Resistance and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as uncertain significance (n-2) or benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000594025	SCV002035007	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000594025	SCV002036116	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001796755	SCV002038213	benign	not specified		no assertion criteria provided	clinical testing