Submissions for variant NM_007078.3(LDB3):c.1867C>A (p.His623Asn)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002967720	SCV003287352	uncertain significance	Myofibrillar myopathy 4	2024-11-11	criteria provided, single submitter	clinical testing	The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*19362C>A in the primary transcript. This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 623 of the LDB3 protein (p.His623Asn). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. 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.
Ambry Genetics	RCV004990947	SCV005612239	uncertain significance	Cardiovascular phenotype	2024-11-30	criteria provided, single submitter	clinical testing	The p.H623N variant (also known as c.1867C>A), located in coding exon 11 of the LDB3 gene, results from a C to A substitution at nucleotide position 1867. The histidine at codon 623 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005239578	SCV005885168	uncertain significance	not specified	2024-12-17	criteria provided, single submitter	clinical testing	Variant summary: LDB3 c.1867C>A (p.His623Asn) results in a conservative amino acid change located in the LIM domain profile (IPR001781) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251470 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1867C>A in individuals affected with Hypertrophic Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2075431). Based on the evidence outlined above, the variant was classified as uncertain significance.