ClinVar Miner

Submissions for variant NM_001105206.3(LAMA4):c.105C>G (p.Asp35Glu)

gnomAD frequency: 0.00001  dbSNP: rs572035776
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute RCV000584772 SCV000692524 uncertain significance Hypertrophic cardiomyopathy 1 2017-03-16 criteria provided, single submitter research The LAMA4 Asp35Glu is a rare variant, being present in the Exome Aggregation Consortium dataset at a low frequency (MAF=0.000035; http://exac.broadinstitute.org/). Computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to have a deleterious effect. We have identified this variant in a male patient with obstructive HCM, the patient survived a cardiac arrest and has no family history of disease. Although variants in LAMA4 has been associated with DCM, there is no evidence to support its role in HCM. In summary, based on limited evidence in the literature and our limited familial data, we classify LAMA4 Asp35Glu as a variant of "uncertain significance".
Ambry Genetics RCV004024648 SCV003909738 uncertain significance Cardiovascular phenotype 2023-03-07 criteria provided, single submitter clinical testing The c.105C>G (p.D35E) alteration is located in exon 2 (coding exon 1) of the LAMA4 gene. This alteration results from a C to G substitution at nucleotide position 105, causing the aspartic acid (D) at amino acid position 35 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM RCV003338673 SCV004047856 uncertain significance Dilated cardiomyopathy 1JJ criteria provided, single submitter clinical testing The missense variant c.105C>G (p.Asp35Glu) in LAMA4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asp35Glu variant has allele frequency 0.001% in gnomAD exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid Asp at position 35 is changed to a Glu changing protein sequence and it might alter its composition and physico-chemical properties. The p.D35E missense variant is predicted to be damaging by SIFT and PolyPhen2. For these reasons, this variant has been classified as Uncertain Significance (VUS).

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