ClinVar Miner

Submissions for variant NM_015702.3(MMADHC):c.240_241insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGGAACATAGGTTTT (p.Asp81delinsPhePhePhePhePhePheXaaXaaXaaXaaLeuThrSerTer)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002871782 SCV003235517 pathogenic Methylmalonic aciduria and homocystinuria type cblD 2022-12-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in MMADHC are known to be pathogenic (PMID: 18385497). This variant has not been reported in the literature in individuals affected with MMADHC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the MMADHC gene (c.240_241ins?), causing a frameshift at codon 81 (p.Asp81fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product.

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