ClinVar Miner

Submissions for variant NM_002437.5(MPV17):c.260AGA[1] (p.Lys88del)

dbSNP: rs267607263
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197566 SCV000251741 pathogenic not provided 2024-09-16 criteria provided, single submitter clinical testing In-frame deletion of 1 amino acid(s) in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20074988, 19748572, 31980526, 34052969, 37184518, 35598585, 29282788, 17694548)
Labcorp Genetics (formerly Invitae), Labcorp RCV000197566 SCV001403711 likely pathogenic not provided 2024-03-27 criteria provided, single submitter clinical testing This variant, c.263_265del, results in the deletion of 1 amino acid(s) of the MPV17 protein (p.Lys88del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs267607263, gnomAD 0.004%). This variant has been observed in individual(s) with mitochondrial DNA depletion syndrome (PMID: 17694548, 29282788; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 38352). This variant disrupts the p.Lys88 amino acid residue in MPV17. Other variant(s) that disrupt this residue have been observed in individuals with MPV17-related conditions (PMID: 20074988), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000031908 SCV001445919 likely pathogenic Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) 2019-05-24 criteria provided, single submitter clinical testing This variant has been previously reported as a compound heterozygous change in patients with hepatocerebral mitochondrial DNA depletion syndrome (PMID: 17694548) and has been classified as Likely Pathogenic by another clinical diagnostic laboratory in the ClinVar database (Variation ID: 38352). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.002% (4/246258) and thus is presumed to be rare. In silico analyses support a deleterious effect of the c.263_265del (p.Lys88del) variant on protein function. Based on the available evidence, the c.263_265del (p.Lys88del) variant is classified as Likely Pathogenic.
Baylor Genetics RCV003466881 SCV004193740 pathogenic Charcot-Marie-Tooth disease, axonal, type 2EE 2024-02-27 criteria provided, single submitter clinical testing
Natera, Inc. RCV000031908 SCV001462526 likely pathogenic Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) 2020-09-16 no assertion criteria provided clinical testing

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