Submissions for variant NM_002693.3(POLG):c.2845_2847del (p.Phe949del)

dbSNP: rs1567186596

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000758314	SCV000886972	uncertain significance	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.2845_2847del (NP_002684.1:p.Phe949del) [GRCH38: NC_000015.10:g.89320902_89320904del] 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. PM1:This variant is in mutational hot spot or a well-studied functional domain without benign variation. PM2:This variant is absent in key population databases. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000758314	SCV001490797	uncertain significance	Progressive sclerosing poliodystrophy	2023-03-14	criteria provided, single submitter	clinical testing	This variant, c.2845_2847del, results in the deletion of 1 amino acid(s) of the POLG protein (p.Phe949del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 619330). This variant has not been reported in the literature in individuals affected with POLG-related conditions.