ClinVar Miner

Submissions for variant NM_194277.3(FRMD7):c.425T>G (p.Leu142Arg)

gnomAD frequency: 0.00001  dbSNP: rs137852211
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001385158 SCV001584919 pathogenic not provided 2023-10-09 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 142 of the FRMD7 protein (p.Leu142Arg). This variant is present in population databases (rs137852211, gnomAD 0.001%). This missense change has been observed in individual(s) with X-linked congenital nystagmus (PMID: 17013395, 18087240). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 10788). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001385158 SCV004014439 likely pathogenic not provided 2024-09-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21904664, 18087240, 17013395)
Clinical Genomics Laboratory, Washington University in St. Louis RCV000011535 SCV004177151 likely pathogenic Nystagmus 1, congenital, X-linked 2023-08-02 criteria provided, single submitter clinical testing The FRMD7 c.425T>G (p.Leu142Arg) variant has been reported in three unrelated families affected with nystagmus, and is reported to segregate with disease in two of these families (Tarpey P et al., PMID: 17013395; Shiels A et al., PMID: 18087240). This variant is only observed on 1/183,350 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors suggest that the variant is damaging, evidence that correlates with impact to FRMD7 function. This variant has been submitted to ClinVar as pathogenic by one laboratory (Variation ID: 10788). Based on available information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely pathogenic.
OMIM RCV000011535 SCV000031767 pathogenic Nystagmus 1, congenital, X-linked 2007-11-29 no assertion criteria provided literature only

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