Submissions for variant NM_007078.3(LDB3):c.1269T>G (p.Asn423Lys)

gnomAD frequency: 0.00001  dbSNP: rs375894985

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002024339	SCV002308712	uncertain significance	Myofibrillar myopathy 4	2022-01-28	criteria provided, single submitter	clinical testing	Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs375894985, gnomAD 0.007%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 423 of the LDB3 protein (p.Asn423Lys). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*16990T>G in the primary transcript.
PreventionGenetics, part of Exact Sciences	RCV003402067	SCV004111375	uncertain significance	LDB3-related disorder	2023-01-11	criteria provided, single submitter	clinical testing	The LDB3 c.939T>G variant is predicted to result in the amino acid substitution p.Asn313Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-88476121-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.