NM_002693.2(POLG):c.3346A>G (p.Met1116Val) AND Progressive sclerosing poliodystrophy

Clinical significance:Uncertain significance (Last evaluated: Apr 11, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000552872.1

Allele description [Variation Report for NM_002693.2(POLG):c.3346A>G (p.Met1116Val)]

NM_002693.2(POLG):c.3346A>G (p.Met1116Val)

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.3346A>G (p.Met1116Val)
Other names:
p.M1116V:ATG>GTG
HGVS:
  • NC_000015.10:g.89318677T>C
  • NG_008218.2:g.21119A>G
  • NM_002693.2:c.3346A>G
  • NP_002684.1:p.Met1116Val
  • LRG_765t1:c.3346A>G
  • LRG_765:g.21119A>G
  • LRG_765p1:p.Met1116Val
  • NC_000015.9:g.89861908T>C
Protein change:
M1116V
Links:
dbSNP: rs201144044
NCBI 1000 Genomes Browser:
rs201144044
Molecular consequence:
  • NM_002693.2:c.3346A>G - 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
SCV000630146Invitaecriteria provided, single submitter
Uncertain significance
(Apr 11, 2017)
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

Citations

PubMed

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, SCV000630146.1

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

Description

This sequence change replaces methionine with valine at codon 1116 of the POLG protein (p.Met1116Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs201144044, ExAC 0.001%) but has not been reported in the literature in individuals with a POLG-related disease. ClinVar contains an entry for this variant (Variation ID: 206561). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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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