Submissions for variant NM_004990.4(MARS1):c.2671C>T (p.Pro891Ser)

gnomAD frequency: 0.00070  dbSNP: rs35843015

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000652561	SCV000774431	likely benign	Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U	2024-01-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001592822	SCV001816248	uncertain significance	not provided	2023-06-15	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Identified in an individual with hereditary spastic paraplegia, but segregation information was not provided (Panwala et al., 2022); This variant is associated with the following publications: (PMID: 35303589)
Ambry Genetics	RCV002461985	SCV002755151	likely benign	Inborn genetic diseases	2019-10-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity	RCV001592822	SCV003808279	uncertain significance	not provided	2021-07-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003937984	SCV004763255	likely benign	MARS1-related condition	2022-04-18	criteria provided, single submitter	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).