ClinVar Miner

Submissions for variant NM_003937.3(KYNU):c.1045_1051del (p.Phe349fs)

dbSNP: rs770642379
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Embryology Laboratory, Victor Chang Cardiac Research Institute RCV000496114 SCV000540923 pathogenic Congenital NAD deficiency disorder 2016-12-23 criteria provided, single submitter research This variant was discovered in a North American family. The patient presented multiple congenital malformations affecting vertebrae, heart, kidney among others. This variant is a protein truncating variant and novel (ExAC MAF 0). The patient is compound heterzygous for this variant and another protein truncating variant in the same KYNU gene (NM_003937.2:c.468T>A). Her unaffected parents are heterzygous for only one variant. Enzyme assay confirmed that the protein product of this gene variant has lost enzyme activity. Mouse embryos homozygous null for Kynu presented similar phenotype as observed in the patient, and also showed reduced concentration of NAD in the embryonic tissue.
GeneDx RCV000520521 SCV000618083 pathogenic not provided 2023-11-07 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Published functional studies demonstrate a damaging effect on enzyme activity (PMID: 28792876); This variant is associated with the following publications: (PMID: 28792876)
Baylor Genetics RCV000505812 SCV004183449 pathogenic Vertebral, cardiac, renal, and limb defects syndrome 2 2023-09-29 criteria provided, single submitter clinical testing
Molecular Genetics, Royal Melbourne Hospital RCV000505812 SCV004812278 pathogenic Vertebral, cardiac, renal, and limb defects syndrome 2 2023-05-05 criteria provided, single submitter clinical testing This sequence change in KYNU is a frameshift variant predicted to cause a premature stop codon, p.(Phe349Lysfs*4), in biologically relevant exon 13/14 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PMID: 28792876). The highest population minor allele frequency in the population database gnomAD v2.1 is 0.006% (8/128,530 alleles) in the European (non-Finnish) population, which is consistent with vertebral, cardiac, renal, and limb defects syndrome. This variant has been detected in an individual with vertebral, cardiac, renal, and limb defects syndrome compound heterozygous with a pathogenic variant and was confirmed in trans by parental testing (PMID: 28792876). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM3, PM2_Supporting.
OMIM RCV000505812 SCV000600002 pathogenic Vertebral, cardiac, renal, and limb defects syndrome 2 2024-03-06 no assertion criteria provided literature only

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