Submissions for variant NM_001031710.3(KLHL7):c.433A>G (p.Asn145Asp)

dbSNP: rs1182983579

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001043815	SCV001207581	pathogenic	not provided	2024-10-21	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 145 of the KLHL7 protein (p.Asn145Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 28041643, 31856884; internal data). ClinVar contains an entry for this variant (Variation ID: 438051). 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. This variant disrupts the p.Asn145 amino acid residue in KLHL7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31856884). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001074657	SCV001240249	likely pathogenic	Retinal dystrophy	2019-02-21	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376512	SCV001573689	uncertain significance	Retinitis pigmentosa 42	2021-04-08	criteria provided, single submitter	research	The KLHL7 c.433A>G variant was identified in an individual with retinitis pigmentosa with a presumed dominant inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PM1, PP3. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
GeneDx	RCV001043815	SCV003803414	likely pathogenic	not provided	2022-08-11	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); 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: 32581362, 31856884, 28041643, 31049658, 32531858)
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001074657	SCV005072398	likely pathogenic	Retinal dystrophy	2018-01-01	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504764	SCV000598878	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research