ClinVar Miner

Submissions for variant NM_001105206.3(LAMA4):c.676C>T (p.Pro226Ser)

gnomAD frequency: 0.00001  dbSNP: rs201820268
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000171985 SCV000050967 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Ambry Genetics RCV002362879 SCV002666510 uncertain significance Cardiovascular phenotype 2020-12-03 criteria provided, single submitter clinical testing The p.P226S variant (also known as c.676C>T), located in coding exon 5 of the LAMA4 gene, results from a C to T substitution at nucleotide position 676. The proline at codon 226 is replaced by serine, an amino acid with similar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort; however, clinical details are limited (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is well conserved in available vertebrate species; however, serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002492718 SCV002782352 uncertain significance Dilated cardiomyopathy 1JJ 2021-09-17 criteria provided, single submitter clinical testing
Invitae RCV002492718 SCV004300450 uncertain significance Dilated cardiomyopathy 1JJ 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 226 of the LAMA4 protein (p.Pro226Ser). This variant is present in population databases (rs201820268, gnomAD 0.002%). 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: 191692). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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