Submissions for variant NM_024753.5(TTC21B):c.2815C>T (p.Arg939Trp)

gnomAD frequency: 0.00036  dbSNP: rs151227843

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000387559	SCV000417615	uncertain significance	Asphyxiating thoracic dystrophy 4	2018-01-12	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.
Illumina Laboratory Services, Illumina	RCV000281585	SCV000417616	uncertain significance	Nephronophthisis 12	2018-01-12	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	RCV000756834	SCV000617036	uncertain significance	not provided	2022-11-02	criteria provided, single submitter	clinical testing	Functional studies suggest this variant results in a non-functional protein, however, the clinical relevance of this is unclear (Davis et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21258341)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756834	SCV000884764	uncertain significance	not provided	2017-11-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001859969	SCV002176786	benign	Jeune thoracic dystrophy; Nephronophthisis	2024-01-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000756834	SCV004147152	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing	TTC21B: PM2, BP4
Breakthrough Genomics, Breakthrough Genomics	RCV000756834	SCV005187985	uncertain significance	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004537838	SCV004736371	likely benign	TTC21B-related disorder	2022-12-14	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).