Submissions for variant NM_024753.5(TTC21B):c.2258C>T (p.Pro753Leu)

gnomAD frequency: 0.00001  dbSNP: rs539769126

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000550901	SCV000630970	benign	Jeune thoracic dystrophy; Nephronophthisis	2024-01-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001128710	SCV001288199	likely benign	Asphyxiating thoracic dystrophy 4	2017-04-27	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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001128711	SCV001288200	uncertain significance	Nephronophthisis 12	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258267	SCV001435190	benign	Meckel-Gruber-like syndrome		criteria provided, single submitter	research	The heterozygous p.Pro753Leu variant in TTC21B has been identified in 2 individuals with Meckel-Gruber-like syndrome (PMID: 21258341), but has also been identified in 5 unaffected individuals (PMID: 21258341), and >1% of South Asian chromosomes and 2 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Pro753Leu variant may silghtly impact protein function (PMID: 21258341). However, these types of assays may not accurately represent biological function. In summary, this variant meets criteria to be classified as benign for autosomal recessive Meckel-Gruber-like syndrome.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572659	SCV001797376	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001572659	SCV001964158	likely benign	not provided		no assertion criteria provided	clinical testing