Submissions for variant NM_001191061.2(SLC25A22):c.679G>A (p.Val227Met)

gnomAD frequency: 0.00024  dbSNP: rs200603610

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721220	SCV000242964	likely benign	not provided	2024-06-03	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000636275	SCV000757714	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 227 of the SLC25A22 protein (p.Val227Met). This variant is present in population databases (rs200603610, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with SLC25A22-related conditions. ClinVar contains an entry for this variant (Variation ID: 207170). 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 not expected to disrupt SLC25A22 protein function with a negative predictive value of 80%. 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.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000678848	SCV000805039	uncertain significance	Macrocephaly; Developmental delay	2017-05-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314763	SCV000848349	uncertain significance	Inborn genetic diseases	2018-06-22	criteria provided, single submitter	clinical testing	The p.V227M variant (also known as c.679G>A), located in coding exon 7 of the SLC25A22 gene, results from a G to A substitution at nucleotide position 679. The valine at codon 227 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV001721220	SCV004033080	uncertain significance	not provided	2023-07-01	criteria provided, single submitter	clinical testing	SLC25A22: PM2:Supporting
Mayo Clinic Laboratories, Mayo Clinic	RCV001721220	SCV005412263	uncertain significance	not provided	2024-08-21	criteria provided, single submitter	clinical testing	PM2_moderate