ClinVar Miner

Submissions for variant NM_014251.3(SLC25A13):c.1048G>A (p.Asp350Asn)

gnomAD frequency: 0.00002  dbSNP: rs1312396424
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001061179 SCV001225912 pathogenic Citrin deficiency 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 350 of the SLC25A13 protein (p.Asp350Asn). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individuals with citrin deficiency (PMID: 20376801, 24069319, 27405544). ClinVar contains an entry for this variant (Variation ID: 855835). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC25A13 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226430 SCV003923053 pathogenic Citrullinemia type II 2023-03-19 criteria provided, single submitter clinical testing Variant summary: SLC25A13 c.1048G>A (p.Asp350Asn) results in a conservative amino acid change located in the Mitochondrial substrate/solute carrier repeat (IPR018108) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251310 control chromosomes (gnomAD). c.1048G>A has been reported in the literature in multiple compound heterozygous individuals affected with Citrullinemia (e.g. Song_2013, Lin_2016, Wang_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic and the other as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV003473677 SCV004201663 likely pathogenic Citrullinemia, type II, adult-onset 2024-03-15 criteria provided, single submitter clinical testing
Royal Medical Services, Bahrain Defence Force Hospital RCV004584421 SCV005068254 pathogenic Neonatal intrahepatic cholestasis due to citrin deficiency criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005036362 SCV005671930 pathogenic Neonatal intrahepatic cholestasis due to citrin deficiency; Citrullinemia, type II, adult-onset 2024-02-12 criteria provided, single submitter clinical testing
Natera, Inc. RCV001832548 SCV002079380 likely pathogenic Citrullinemia 2021-05-21 no assertion criteria provided clinical testing

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