Submissions for variant NM_007078.3(LDB3):c.1601_1602dup (p.Thr535fs)

dbSNP: rs1846890164

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001246801	SCV001420186	uncertain significance	Myofibrillar myopathy 4	2019-07-30	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. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in LDB3 cause disease. This variant has not been reported in the literature in individuals with LDB3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr535Glyfs*31) in the LDB3 gene. It is expected to result in an absent or disrupted protein product. The LDB3 gene has multiple clinically relevant transcripts. The p.Thr535Glyfs*31 variant occurs in alternate transcript NM_007078.2, which corresponds to c.*17322_*17323dup in NM_001080116.1, the primary transcript listed in the Methods.
GeneDx	RCV001568761	SCV001792687	uncertain significance	not provided	2019-07-26	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease; Only missense variants in LDB3 have been reported in HGMD in association with cardiac disease (Stenson et al., 2014)
Ambry Genetics	RCV002402786	SCV002708658	uncertain significance	Cardiovascular phenotype	2022-04-07	criteria provided, single submitter	clinical testing	The c.1601_1602dupGG variant, located in coding exon 9 of the LDB3 gene, results from a duplication of GG at nucleotide position 1601, causing a translational frameshift with a predicted alternate stop codon (p.T535Gfs*31). This alteration is expected to result in premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of LDB3 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.