Submissions for variant NM_001349.4(DARS1):c.1088G>A (p.Gly363Glu)

gnomAD frequency: 0.00113  dbSNP: rs2228660

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523420	SCV000618325	uncertain significance	not provided	2017-10-19	criteria provided, single submitter	clinical testing	The G363E variant has been detected by whole exome sequencing as homozygous in an individual with multiple congenital anomalies who also had maternal uniparental disomy of chromosome 2 (Carmichael et al., 2013). The G363E variant is observed in 99/24,016 (0.4%) alleles from individuals of African background, in large population cohorts, although no homozygous individuals were reported (Lek et al., 2016). The G363E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000523420	SCV002510655	likely benign	not provided	2025-01-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003942711	SCV004758978	likely benign	DARS1-related disorder	2022-06-01	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).