ClinVar Miner

Submissions for variant NM_004279.3(PMPCB):c.601G>C (p.Ala201Pro)

gnomAD frequency: 0.00005  dbSNP: rs146343535
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001267318 SCV001445499 likely pathogenic Inborn genetic diseases 2021-10-06 criteria provided, single submitter clinical testing The c.601G>C (p.A201P) alteration is located in coding exon 5 of the PMPCB gene. This alteration results from a G to C substitution at nucleotide position 601, causing the alanine (A) at amino acid position 201 to be replaced by a proline (P). Based on data from gnomAD, the C allele has an overall frequency of <0.01% (9/282768) total alleles studied. This alteration has been reported, in trans with c.523C>T (p.R175C), in two affected individuals with developmental regression, seizures, abnormal brain MRI, elevated serum lactate, and inability to walk (V&ouml;gtle, 2018). This amino acid position is highly conserved in available vertebrate species. Functional analysis of the yeast Mas1 homologous p.A201P alteration showed a defect in mitochondrial precursor processing under heat shock. Additionally, muscle biopsy from one affected individual heterozygous for this variant in trans with c.523C>T (p.R175C) showed severely decreased complex II activity, as well as deficient activity of both the cytosolic and mitochondrial aconitase enzymes (V&ouml;gtle, 2018). The in silico prediction for this alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV002221567 SCV002499055 uncertain significance not provided 2022-02-16 criteria provided, single submitter clinical testing PM2, PP3
OMIM RCV000626412 SCV000747103 pathogenic Multiple mitochondrial dysfunctions syndrome 6 2018-08-29 no assertion criteria provided literature only

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