NM_002693.2(POLG):c.488C>T (p.Pro163Leu) AND Progressive sclerosing poliodystrophy

Clinical significance:Uncertain significance (Last evaluated: May 2, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000633534.2

Allele description [Variation Report for NM_002693.2(POLG):c.488C>T (p.Pro163Leu)]

NM_002693.2(POLG):c.488C>T (p.Pro163Leu)

Gene:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.2(POLG):c.488C>T (p.Pro163Leu)
Other names:
p.P163L:CCC>CTC
HGVS:
  • NC_000015.10:g.89333267G>A
  • NG_008218.2:g.6529C>T
  • NM_002693.2:c.488C>T
  • NP_002684.1:p.Pro163Leu
  • LRG_765t1:c.488C>T
  • LRG_765:g.6529C>T
  • LRG_765p1:p.Pro163Leu
  • NC_000015.9:g.89876498G>A
Protein change:
P163L
Links:
dbSNP: rs752892262
NCBI 1000 Genomes Browser:
rs752892262
Molecular consequence:
  • NM_002693.2:c.488C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000754780Invitaecriteria provided, single submitter
Uncertain significance
(May 2, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

POLG mutations in Australian patients with mitochondrial disease.

Woodbridge P, Liang C, Davis RL, Vandebona H, Sue CM.

Intern Med J. 2013 Feb;43(2):150-6. doi: 10.1111/j.1445-5994.2012.02847.x.

PubMed [citation]
PMID:
22647225

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]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000754780.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces proline with leucine at codon 163 of the POLG protein (p.Pro163Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a POLG-related disease. ClinVar contains an entry for this variant (Variation ID: 206579). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Pro163Ser) has been reported in the literature in an individual affected with POLG-related diseases (PMID: 22647225), however, the clinical significance of this variant is 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.

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

Last Updated: Apr 17, 2019

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