ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.2704C>G (p.Leu902Val)

gnomAD frequency: 0.00003  dbSNP: rs745528696
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000728575 SCV000856167 uncertain significance not provided 2017-08-04 criteria provided, single submitter clinical testing
Invitae RCV001052151 SCV001216348 uncertain significance Progressive sclerosing poliodystrophy 2022-10-18 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 902 of the POLG protein (p.Leu902Val). This variant is present in population databases (rs745528696, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 593514). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt POLG protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002485861 SCV002794396 uncertain significance Progressive sclerosing poliodystrophy; Mitochondrial DNA depletion syndrome 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4b 2021-08-23 criteria provided, single submitter clinical testing
GeneDx RCV000728575 SCV002818782 uncertain significance not provided 2023-01-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002535079 SCV003640730 uncertain significance Inborn genetic diseases 2021-08-10 criteria provided, single submitter clinical testing The c.2704C>G (p.L902V) alteration is located in exon 17 (coding exon 16) of the POLG gene. This alteration results from a C to G substitution at nucleotide position 2704, causing the leucine (L) at amino acid position 902 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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