Submissions for variant NM_018718.3(CEP41):c.107T>C (p.Met36Thr)

gnomAD frequency: 0.00011  dbSNP: rs368178632

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000268974	SCV000466830	uncertain significance	Joubert syndrome 15	2016-09-28	criteria provided, single submitter	clinical testing	The CEP41 c.107T>C (p.Met36Thr) variant is a missense variant that has been reported in a heterozygous state in one individual with Joubert syndrome (JS) who also carried a second heterozygous variant in another JS-associated gene (Lee et al. 2012). Digenic inheritance of JS has been previously reported (Parisi et al. 2013). Control data are unavailable for this variant, which is reported at a frequency of 0.00014 in the European (non-Finnish) population of the Exome Aggregation Consortium. The evidence for this variant is limited. The p.Met36Thr variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for Joubert syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae	RCV000268974	SCV001223530	uncertain significance	Joubert syndrome 15	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 36 of the CEP41 protein (p.Met36Thr). This variant is present in population databases (rs368178632, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of a ciliopathy spectrum disorder (PMID: 22246503). This variant is also known as p.36M>T. ClinVar contains an entry for this variant (Variation ID: 30842). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CEP41 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001544767	SCV001763963	uncertain significance	not provided	2020-07-27	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30664616, 22246503)
Fulgent Genetics, Fulgent Genetics	RCV000268974	SCV002778599	uncertain significance	Joubert syndrome 15	2022-02-03	criteria provided, single submitter	clinical testing
OMIM	RCV000023827	SCV000045118	pathogenic	Joubert syndrome 9/15, digenic	2012-01-15	no assertion criteria provided	literature only
University of Washington Center for Mendelian Genomics, University of Washington	RCV001261715	SCV001439024	likely pathogenic	Familial Autism Spectrum Disorder		no assertion criteria provided	research
Clinical Genetics, Academic Medical Center	RCV001544767	SCV002034684	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001544767	SCV002037792	uncertain significance	not provided		no assertion criteria provided	clinical testing