Submissions for variant NM_007078.3(LDB3):c.184C>T (p.His62Tyr)

dbSNP: rs779234633

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000494440	SCV000582350	uncertain significance	not provided	2017-05-12	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the LDB3 gene. The H62Y variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The H62Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function
Invitae	RCV003766776	SCV004676799	uncertain significance	Myofibrillar myopathy 4	2023-07-03	criteria provided, single submitter	clinical testing	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. 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. ClinVar contains an entry for this variant (Variation ID: 429716). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs779234633, gnomAD 0.0009%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 62 of the LDB3 protein (p.His62Tyr).