Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000193784 | SCV000249138 | likely benign | not specified | 2021-02-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001088798 | SCV000562433 | likely benign | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000726711 | SCV000577323 | uncertain significance | not provided | 2018-09-04 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TCTN1 gene. The c.702_704delTAA variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.702_704delTAA variant is observed in 168/66,738 (0.3%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.702_704delTAA results in an in-frame deletion of a single Asparagine residue, denoted p.Asn235del. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Eurofins Ntd Llc |
RCV000726711 | SCV000702323 | uncertain significance | not provided | 2016-10-21 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002517143 | SCV003696630 | likely benign | Inborn genetic diseases | 2022-04-19 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Prevention |
RCV003927810 | SCV004744690 | likely benign | TCTN1-related condition | 2022-02-03 | criteria provided, single submitter | 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). |
Department of Pathology and Laboratory Medicine, |
RCV000726711 | SCV001550005 | likely benign | not provided | no assertion criteria provided | clinical testing | The TCTN1 p.Asn235del variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs1179582623) and ClinVar (classified as uncertain significance by Genetic Services Laboratory, University of Chicago, EGL Genetic Diagnostics and GeneDx, and as likely benign by Invitae). The variant was identified in control databases in 455 of 280942 chromosomes (2 homozygous) at a frequency of 0.00162 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 420 of 128690 chromosomes (freq: 0.003264), Other in 7 of 7148 chromosomes (freq: 0.000979), European (Finnish) in 12 of 25030 chromosomes (freq: 0.000479), African in 11 of 24202 chromosomes (freq: 0.000455) and Latino in 5 of 35374 chromosomes (freq: 0.000141), but was not observed in the Ashkenazi Jewish, East Asian, or South Asian populations. This variant is an in-frame deletion resulting in the removal of a asparagine (asn) residue at codon 235; the impact of this alteration on TCTN1 protein function is not known. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |