Submissions for variant NM_001040716.2(PC):c.1512C>T (p.Leu504=)

gnomAD frequency: 0.00006  dbSNP: rs763298490

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000815111	SCV000955555	uncertain significance	Pyruvate carboxylase deficiency	2018-07-30	criteria provided, single submitter	clinical testing	This sequence change affects codon 504 of the PC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PC protein. This variant is present in population databases (rs763298490, ExAC 0.006%). This variant has not been reported in the literature in individuals with PC-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003222142	SCV003916738	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	PC: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003955524	SCV004770586	likely benign	PC-related condition	2020-02-19	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).