Submissions for variant NM_007078.3(LDB3):c.1388C>A (p.Pro463His)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002396586	SCV002699049	uncertain significance	Cardiovascular phenotype	2023-10-12	criteria provided, single submitter	clinical testing	The p.P463H variant (also known as c.1388C>A), located in coding exon 9 of the LDB3 gene, results from a C to A substitution at nucleotide position 1388. The proline at codon 463 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV003502664	SCV004300993	uncertain significance	Myofibrillar myopathy 4	2023-01-04	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 463 of the LDB3 protein (p.Pro463His). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17109C>A in the primary transcript.
PreventionGenetics, part of Exact Sciences	RCV003926384	SCV004741773	uncertain significance	LDB3-related disorder	2023-10-28	criteria provided, single submitter	clinical testing	The LDB3 c.1058C>A variant is predicted to result in the amino acid substitution p.Pro353His. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.