Submissions for variant NM_001349.4(DARS1):c.590G>A (p.Arg197His)

gnomAD frequency: 0.00244  dbSNP: rs141522501

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522019	SCV000618204	uncertain significance	not provided	2017-10-19	criteria provided, single submitter	clinical testing	The R197H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R197H variant is observed in 83/10,002 (0.8%) of alleles from individuals of Ashkenazi Jewish background including one individual who was apparently homozygous for R197H (Lek et al., 2016). The R197H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar 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	RCV000522019	SCV001055253	likely benign	not provided	2023-12-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000522019	SCV002544069	benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	DARS1: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003925558	SCV004752859	benign	DARS1-related disorder	2019-07-10	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).