Submissions for variant NM_000355.4(TCN2):c.296A>C (p.Lys99Thr)

gnomAD frequency: 0.00135  dbSNP: rs150225103

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000635260	SCV000756648	likely benign	Transcobalamin II deficiency	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000635260	SCV001309419	uncertain significance	Transcobalamin II deficiency	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, 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.
GeneDx	RCV001771857	SCV001993854	uncertain significance	not provided	2019-05-13	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000635260	SCV004563356	uncertain significance	Transcobalamin II deficiency	2023-08-10	criteria provided, single submitter	clinical testing	The TCN2 c.296A>C; p.Lys99Thr variant (rs150225103), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 529780). This variant is found in the African/African-American population with an allele frequency of 0.38% (96/24,958 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.209). Due to limited information, the clinical significance of this variant is uncertain at this time.
PreventionGenetics, part of Exact Sciences	RCV004754514	SCV005346685	likely benign	TCN2-related disorder	2024-06-19	no assertion criteria provided	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).