ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.2674dup (p.Asp892fs)

dbSNP: rs1283198587
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758274 SCV000886926 pathogenic Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.2674dup (NP_002684.1:p.Asp892GlyfsTer?) [GRCH38: NC_000015.10:g.89321186dup] variant in POLG gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. PVS1:This variant is a predicted null variant in POLG where loss of function is a known mechanism of disease. PM2:This variant is absent in key population databases. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 4A (Alpers type) which is a recessive disorder. PM4:This variant causes alteration in the length of expressed protein. PP1:This variant is co-segregated with Mitochondrial DNA depletion syndrome 4A (Alpers type) in multiple affected family members. PP4:Patient's phenotype or family history is highly specific for POLG. Based on the evidence criteria codes applied, the variant is suggested to be Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000758274 SCV003443007 pathogenic Progressive sclerosing poliodystrophy 2022-10-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 619306). This premature translational stop signal has been observed in individual(s) with clinical features of POLG-related conditions (PMID: 21880868). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp892Glyfs*39) in the POLG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POLG are known to be pathogenic (PMID: 18546365).

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