ClinVar Miner

Submissions for variant NM_005506.4(SCARB2):c.432_433AG[3] (p.Trp146fs) (rs727502773)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188810 SCV000242434 pathogenic not provided 2016-03-22 criteria provided, single submitter clinical testing c.434_435dupAG: p.Trp146SerfsX16 (W146SfsX16) in exon 4 of the SCARB2 gene (NM_005506.3). The normal sequence with the bases that are duplicated in braces is: ATAG{AG}TGGT.The c.434_435dupAG variant in the SCARB2 gene has been reported previously in association with action myoclonus-renal failure syndrome (AMRF) (Berkovic et al., 2008). The duplication causes a frameshift starting with codon Tryptophan 146, changes this amino acid to a Serine residue and creates a premature Stop codon at position 16 of the new reading frame, denoted p.Trp146SerfsX16. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, c.434_435dupAG is considered a pathogenic variant. The variant is found in SCARB2, EPILEPSYV2-1 panel(s).
Invitae RCV001203979 SCV001375164 pathogenic Progressive myoclonic epilepsy 2019-06-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp146Serfs*16) in the SCARB2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs727502773, ExAC 0.01%). This variant has been observed in an individual affected with action myoclonus-renal failure syndrome (PMID: 18308289). It is also known as c.435_436insAG in the literature. ClinVar contains an entry for this variant (Variation ID: 7377). Loss-of-function variants in SCARB2 are known to be pathogenic (PMID: 19847901). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007802 SCV000028003 pathogenic Epilepsy, progressive myoclonic 4, with or without renal failure 2008-03-01 no assertion criteria provided literature only
GeneReviews RCV000007802 SCV000328630 pathogenic Epilepsy, progressive myoclonic 4, with or without renal failure 2015-03-05 no assertion criteria provided literature only

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