Submissions for variant NM_014251.3(SLC25A13):c.1945G>C (p.Gly649Arg)

gnomAD frequency: 0.00013  dbSNP: rs757317844

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000271327	SCV000470697	uncertain significance	Citrullinemia type I	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001095212	SCV000470698	uncertain significance	Citrullinemia type II	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.
Eurofins Ntd Llc (ga)	RCV000593765	SCV000703849	uncertain significance	not provided	2017-01-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000328760	SCV000826930	uncertain significance	Citrin deficiency	2022-07-18	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 649 of the SLC25A13 protein (p.Gly649Arg). This variant is present in population databases (rs757317844, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SLC25A13-related conditions. ClinVar contains an entry for this variant (Variation ID: 361010). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
Ambry Genetics	RCV003168565	SCV003880175	uncertain significance	Inborn genetic diseases	2023-02-16	criteria provided, single submitter	clinical testing	The c.1945G>C (p.G649R) alteration is located in exon 18 (coding exon 18) of the SLC25A13 gene. This alteration results from a G to C substitution at nucleotide position 1945, causing the glycine (G) at amino acid position 649 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
3billion, Medical Genetics	RCV004725186	SCV005328878	likely benign	Neonatal intrahepatic cholestasis due to citrin deficiency; Citrullinemia, type II, adult-onset	2024-09-20	criteria provided, single submitter	clinical testing	The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.
Natera, Inc.	RCV001277318	SCV001464260	uncertain significance	Late-onset citrullinemia	2020-01-17	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004742402	SCV005354046	uncertain significance	SLC25A13-related disorder	2024-09-10	no assertion criteria provided	clinical testing	The SLC25A13 c.1945G>C variant is predicted to result in the amino acid substitution p.Gly649Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.028% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.