ClinVar Miner

Submissions for variant NM_173477.5(USH1G):c.83C>T (p.Pro28Leu) (rs145448362)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041427 SCV000065122 uncertain significance not specified 2020-04-07 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Pro28Leu variant in USH1G has been reported in the heterozygous state in two individuals with Usher syndrome type 2 (Aller 2007), one individual with retinitis pigmentosa (Haer-Wigman, 2017), and three children with apparently nonsyndromic hearing loss (LMM data). It has also been identified in 0.15% (138/91578) of Europeans chromosomes by gnomAD ( and has been reported as likely benign by a clinical lab in ClinVar (Variation ID 48139). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of this variant is uncertain, its frequency suggests that it is more likely to be benign. ACMG/AMP Criteria applied: BS1_Supporting.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000432648 SCV000510711 uncertain significance not provided 2017-01-25 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
GeneDx RCV000432648 SCV000970667 likely benign not provided 2020-05-12 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 17896313, 28224992)
Invitae RCV000432648 SCV001234492 uncertain significance not provided 2020-01-03 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 28 of the USH1G protein (p.Pro28Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs145448362, ExAC 0.2%). This variant has been observed in individuals affected with Usher syndrome or retinitis pigmentosa (PMID: 28224992, 17896313, 22135276). ClinVar contains an entry for this variant (Variation ID: 48139). 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"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV001127509 SCV001286824 uncertain significance Usher syndrome, type 1G 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Human Genetics - Radboudumc,Radboudumc RCV000432648 SCV001953701 uncertain significance not provided no assertion criteria provided clinical testing

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