ClinVar Miner

Submissions for variant NM_005957.4(MTHFR):c.1530G>A (p.Lys510=) (rs765586205)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000546103 SCV000641853 pathogenic Homocysteinemia due to MTHFR deficiency 2018-02-05 criteria provided, single submitter clinical testing This sequence change affects codon 510 of the MTHFR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MTHFR protein. This variant also falls at the last nucleotide of exon 9 of the MTHFR coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs765586205, ExAC 0.03%). This is the most common MTHFR-deficiency variant and it has been reported in the literature in multiple individuals and families affected with homocystinuria (PMID: 24997712, 22887477, 26898294, 26872964, 25736335). This variant is also known in the literature as p.Lys510=. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this silent variant causes a splicing defect that results in skipping of exon 8 resulting in a frameshift and premature termination of the protein (PMID: 25736335). For these reasons, this variant has been classified as Pathogenic.

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