Submissions for variant NM_000370.3(TTPA):c.663+11T>C

gnomAD frequency: 0.59337  dbSNP: rs4501570

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000322713	SCV000474654	benign	Familial isolated deficiency of vitamin E	2018-01-12	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586544	SCV000696611	benign	not provided	2016-12-18	criteria provided, single submitter	clinical testing	Variant summary: The TTPA c.663+11T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools via Alamut suggest no significant impact on a normal splicing pattern, however the functional studies confirming these predictions are yet to be conducted. This variant is present in EXAC at a frequency of 0.59 (63955/107728control chrs). The variant of interest is cites as Benign by reputable databases/clinical diagnostic laboratories. Taken together, based on the frequency in the general population, the variant was classified as Benign.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000322713	SCV000744348	benign	Familial isolated deficiency of vitamin E	2015-09-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000586544	SCV001720945	benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000322713	SCV001762588	benign	Familial isolated deficiency of vitamin E	2021-07-10	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000586544	SCV005268433	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000322713	SCV000734615	benign	Familial isolated deficiency of vitamin E		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001723964	SCV001959538	benign	not specified		no assertion criteria provided	clinical testing