NM_002693.2(POLG):c.3316G>T (p.Val1106Phe) AND Progressive sclerosing poliodystrophy

Clinical significance:Uncertain significance (Last evaluated: Mar 29, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_002693.2(POLG):c.3316G>T (p.Val1106Phe)]

NM_002693.2(POLG):c.3316G>T (p.Val1106Phe)

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_002693.2(POLG):c.3316G>T (p.Val1106Phe)
  • NC_000015.10:g.89318707C>A
  • NG_008218.2:g.21089G>T
  • NM_002693.2:c.3316G>T
  • NP_002684.1:p.Val1106Phe
  • LRG_765t1:c.3316G>T
  • LRG_765:g.21089G>T
  • LRG_765p1:p.Val1106Phe
  • NC_000015.9:g.89861938C>A
Protein change:
Molecular consequence:
  • NM_002693.2:c.3316G>T - missense variant - [Sequence Ontology: SO:0001583]


Progressive sclerosing poliodystrophy (MTDPS4A)
Alpers Syndrome; Mitochondrial DNA depletion syndrome 4A (Alpers type); Alpers-Huttenlocher Syndrome
MedGen: C0205710; Orphanet: 726; OMIM: 203700

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000827285Invitaecriteria provided, single submitter
Uncertain significance
(Mar 29, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11.

PubMed [citation]

Details of each submission

From Invitae, SCV000827285.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)


This sequence change replaces valine with phenylalanine at codon 1106 of the POLG protein (p.Val1106Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POLG-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

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