ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.10342G>A (p.Glu3448Lys) (rs368049814)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000191142 SCV000245551 uncertain significance Retinitis pigmentosa 39 2013-04-10 criteria provided, single submitter clinical testing This variant was found once in our laboratory with a pathogenic variant [E767fs] and another missense variant [G2224C; phase undetermined] in a 32-year-old female with retinitis pigmentosa. Variant possibly pathogenic in recessive state; heterozygotes would be carriers.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000484923 SCV000339979 likely pathogenic not provided 2016-04-04 criteria provided, single submitter clinical testing
GeneDx RCV000484923 SCV000565649 likely pathogenic not provided 2014-11-06 criteria provided, single submitter clinical testing The E3448K variant in the USH2A gene has been reported previously in a patient with Usher syndrome type II and classified as likely benign" based on in silico algorithms; however, other variants listed as "likely benign" based on in silico analysis only had been reported previously as pathogenic variants (McGee et al., 2010). This variant is a non-conservative amino acid substitution of a negatively charged Glutamic aicd with a positively charged Lysine at a residue that is conserved across mammalian species. The E3448K variant was not observed at any significant frequency in approximately 6,000 individuals of European and African American ancestry by an external variant database. The E3448K variant is a good candidate for a pathogenic variant; however, the possibility it may be a rare benign variant cannot be excluded."
Counsyl RCV000675180 SCV000800809 likely pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2018-04-17 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000484923 SCV001147669 likely pathogenic not provided 2019-05-01 criteria provided, single submitter clinical testing
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV001002723 SCV001156416 pathogenic Usher syndrome, type 2A 2019-02-01 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073310 SCV001238848 pathogenic Retinal dystrophy 2018-11-09 criteria provided, single submitter clinical testing
Invitae RCV000484923 SCV001403149 pathogenic not provided 2019-11-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 3448 of the USH2A protein (p.Glu3448Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs368049814, ExAC 0.01%). This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 24265693, 26667666, 28981474, 28761320). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 209203). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504830 SCV000598761 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research

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