Submissions for variant NM_206933.4(USH2A):c.14287G>A (p.Gly4763Arg) (rs397517990)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000041756	SCV000065452	likely pathogenic	Rare genetic deafness	2010-09-27	criteria provided, single submitter	clinical testing	The Gly4763Arg variant in USH2A has been reported in an individual with Usher sy ndrome and in an individual with nonsyndromic retinitis pigmentosa (McGee 2010). In addition, this residue is conserved in mammals. Furthermore, we have identif ied the Gly4763Arg variant in combination with a pathogenic USH2A variant in two siblings with Usher syndrome. In summary, this variant is likely to be pathogen ic.
Counsyl	RCV000665736	SCV000789903	likely pathogenic	Usher syndrome, type 2A; Retinitis pigmentosa 39	2017-10-09	criteria provided, single submitter	clinical testing
Invitae	RCV001057445	SCV001221940	pathogenic	not provided	2019-12-18	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with arginine at codon 4763 of the USH2A protein (p.Gly4763Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals affected with Usher syndrome (PMID: 25649381, 27460420) and also segregated with Usher syndrome in a family. ClinVar contains an entry for this variant (Variation ID: 48433). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana	RCV001198544	SCV001369522	likely pathogenic	Retinal dystrophy; Macular drusen	2019-10-28	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this varinat's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: BP4. This variant was detected in heterozygous state.

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