Submissions for variant NM_002693.3(POLG):c.1898A>C (p.Lys633Thr)

gnomAD frequency: 0.00001  dbSNP: rs568913937

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000188670	SCV000242294	likely benign	not specified	2017-10-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000551532	SCV000630117	benign	Progressive sclerosing poliodystrophy	2024-01-21	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000732615	SCV000860590	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000551532	SCV000887152	uncertain significance	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.1898A>C (NP_002684.1:p.Lys633Thr) [GRCH38: NC_000015.10:g.89325501T>G] variant in POLG gene is interpretated to be a Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. BP4:Computational evidence/predictors indicate no impact on the POLG structure, function, or protein-protein interaction. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.
Illumina Laboratory Services, Illumina	RCV001116517	SCV001274610	uncertain significance	POLG-Related Spectrum Disorders	2018-01-13	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.
Revvity Omics, Revvity	RCV000732615	SCV004237864	likely benign	not provided	2023-11-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000732615	SCV004699659	uncertain significance	not provided	2023-12-01	criteria provided, single submitter	clinical testing	POLG: PM1, BS1:Supporting
PreventionGenetics, part of Exact Sciences	RCV003985762	SCV004726117	likely benign	POLG-related disorder	2023-01-09	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).