Submissions for variant NM_001105206.3(LAMA4):c.1960-3T>C

gnomAD frequency: 0.00006  dbSNP: rs373682270

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000428078	SCV000531157	likely benign	not specified	2016-08-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000651429	SCV000773280	uncertain significance	Dilated cardiomyopathy 1JJ	2017-12-17	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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with LAMA4-related disease. ClinVar contains an entry for this variant (Variation ID: 388786). This variant is present in population databases (rs373682270, ExAC 0.006%). This sequence change falls in intron 15 of the LAMA4 gene. It does not directly change the encoded amino acid sequence of the LAMA4 protein, but it affects a nucleotide within the consensus splice site of the intron.
Ambry Genetics	RCV002411382	SCV002719271	uncertain significance	Cardiovascular phenotype	2019-07-08	criteria provided, single submitter	clinical testing	The c.1939-3T>C intronic variant results from a T to C substitution 3 nucleotides upstream from coding exon 15 in the LAMA4 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor/donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GenomeConnect, ClinGen	RCV001249444	SCV001423455	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 07-08-2019 by Lab or GTR ID 61756. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.