Submissions for variant NM_002693.3(POLG):c.125_139del (p.Arg42_Gln46del)

dbSNP: rs780010436

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705186	SCV000834171	uncertain significance	Progressive sclerosing poliodystrophy	2024-11-12	criteria provided, single submitter	clinical testing	This variant, c.125_139del, results in the deletion of 5 amino acid(s) of the POLG protein (p.Arg42_Gln46del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 581378). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Eurofins Ntd Llc (ga)	RCV000727691	SCV000855032	uncertain significance	not provided	2017-10-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003985807	SCV004795662	likely benign	POLG-related disorder	2023-10-24	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).