Submissions for variant NM_025099.6(CTC1):c.2478A>G (p.Thr826=)

gnomAD frequency: 0.00136  dbSNP: rs200643329

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231025	SCV000290907	benign	Dyskeratosis congenita	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000231025	SCV000407599	uncertain significance	Dyskeratosis congenita	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.
Genetic Services Laboratory, University of Chicago	RCV000501561	SCV000594246	benign	not specified	2017-12-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001573147	SCV001816433	likely benign	not provided	2019-07-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001807147	SCV002055631	likely benign	Cerebroretinal microangiopathy with calcifications and cysts 1	2021-07-15	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001807147	SCV003919861	likely benign	Cerebroretinal microangiopathy with calcifications and cysts 1	2023-01-18	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.2% [72/34082]; https://gnomad.broadinstitute.org/variant/17-8134785-T-C?dataset=gnomad_r2_1). This variant is present in ClinVar, with several labs classifying this variant as Likely Benign or Benign (Variation ID: 241581). Evolutionary conservation and computational prediction tools for this variant are limited or unavailable. Of note, this is a silent variant and does not change the amino acid, reducing the probability that this variant is disease-causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573147	SCV001798572	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573147	SCV001970614	likely benign	not provided		no assertion criteria provided	clinical testing