Submissions for variant NM_024753.5(TTC21B):c.880G>T (p.Ala294Ser)

gnomAD frequency: 0.00048  dbSNP: rs141240501

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000804050	SCV000943942	likely benign	Jeune thoracic dystrophy; Nephronophthisis	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001135928	SCV001295740	uncertain significance	Nephronophthisis 12	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.
Illumina Laboratory Services, Illumina	RCV001135929	SCV001295741	uncertain significance	Asphyxiating thoracic dystrophy 4	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.
Fulgent Genetics, Fulgent Genetics	RCV002487713	SCV002792092	uncertain significance	Asphyxiating thoracic dystrophy 4; Nephronophthisis 12	2022-02-16	criteria provided, single submitter	clinical testing
GeneDx	RCV003128708	SCV003805369	uncertain significance	not provided	2023-02-02	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33323469, 32173348, 36263627)
PreventionGenetics, part of Exact Sciences	RCV004735811	SCV005359677	uncertain significance	TTC21B-related disorder	2024-08-16	no assertion criteria provided	clinical testing	The TTC21B c.880G>T variant is predicted to result in the amino acid substitution p.Ala294Ser. This variant was reported along with a second variant in an individual with nephronophthisis and atypical focal segmental glomerulosclerosis, although pathogenicity was not established (Yue et al. 2020. PubMed ID: 32173348). This variant is reported in 0.21% of alleles in individuals of East Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.