ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1270A>G (p.Thr424Ala)

gnomAD frequency: 0.00001  dbSNP: rs1166140426
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000796032 SCV000935523 uncertain significance Charcot-Marie-Tooth disease type 2 2024-06-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 424 of the LMNA protein (p.Thr424Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 642551). 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 alanine 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001509064 SCV001715574 uncertain significance not provided 2019-10-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV002370085 SCV002683703 uncertain significance Cardiovascular phenotype 2020-03-19 criteria provided, single submitter clinical testing The p.T424A variant (also known as c.1270A>G), located in coding exon 7 of the LMNA gene, results from an A to G substitution at nucleotide position 1270. The threonine at codon 424 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly conserved in available 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.
Color Diagnostics, LLC DBA Color Health RCV003532264 SCV004359116 likely benign Cardiomyopathy 2025-03-24 criteria provided, single submitter clinical testing

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