ClinVar Miner

Submissions for variant NM_004484.3(GPC3):c.595C>T (p.Arg199Ter) (rs104894855)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579176 SCV000680526 pathogenic not provided 2016-12-05 criteria provided, single submitter clinical testing The R199X pathogenic variant in the GPC3 gene has been reported previously in association with Simpson-Golabi-Behmel syndrome in a patient who had pre- and postnatal overgrowth, characteristic facial features, bilateral postaxial polydactyly and bilateral accessory nipples (Veugelers et al., 2000). This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R199X mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R199X as a pathogenic variant. The variant has been observed to be maternally inherited.
Invitae RCV000692634 SCV000820467 pathogenic Wilms tumor 1 2019-03-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg199*) in the GPC3 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individua affected with Simpson-Golabi-Behmel syndrome (PMID: 10814714). ClinVar contains an entry for this variant (Variation ID: 11689). Loss-of-function variants in GPC3 are known to be pathogenic (PMID: 12713262, 17603795). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012455 SCV000032689 pathogenic Simpson-Golabi-Behmel syndrome 2000-05-22 no assertion criteria provided literature only

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