Submissions for variant NM_003332.4(TYROBP):c.46C>T (p.Leu16=)

gnomAD frequency: 0.00121  dbSNP: rs147393700

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000907954	SCV001052687	benign	not provided	2025-01-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001122155	SCV001280851	uncertain significance	Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 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	RCV000907954	SCV003925813	uncertain significance	not provided	2022-11-18	criteria provided, single submitter	clinical testing	In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen	RCV000907954	SCV005434604	likely benign	not provided	2024-10-01	criteria provided, single submitter	clinical testing	TYROBP: BP4, BP7, BS2
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000907954	SCV002035190	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000907954	SCV002036423	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003923107	SCV004738459	likely benign	TYROBP-related disorder	2023-12-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).