ClinVar Miner

Submissions for variant NM_001105206.3(LAMA4):c.4111A>C (p.Ile1371Leu)

gnomAD frequency: 0.00001  dbSNP: rs974775253
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000436535 SCV000529423 uncertain significance not provided 2020-01-31 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV000814418 SCV000954828 uncertain significance Dilated cardiomyopathy 1JJ 2024-05-07 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1364 of the LAMA4 protein (p.Ile1364Leu). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 387395). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000814418 SCV001160222 uncertain significance Dilated cardiomyopathy 1JJ 2019-02-19 criteria provided, single submitter clinical testing The p.Ile1364Leu variant (rs974775253) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.0007 percent (identified on 2 out of 269,746 chromosomes) and has been reported to the ClinVar database (Variation ID: 387395). The isoleucine at position 1364 is highly conserved and computational analyses of the effects of the p.Ile1364Leu variant on protein structure and function is deleterious (SIFT: damaging, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Ile1364Leu variant with certainty.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170686 SCV001333280 uncertain significance Cardiomyopathy 2018-02-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV002323634 SCV002628326 uncertain significance Cardiovascular phenotype 2023-04-25 criteria provided, single submitter clinical testing The c.4090A>C (p.I1364L) alteration is located in exon 30 (coding exon 29) of the LAMA4 gene. This alteration results from a A to C substitution at nucleotide position 4090, causing the isoleucine (I) at amino acid position 1364 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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