Submissions for variant NM_170707.4(LMNA):c.388G>T (p.Ala130Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
All of Us Research Program, National Institutes of Health	RCV004015390	SCV004834270	uncertain significance	Primary dilated cardiomyopathy	2023-12-13	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with serine at codon 130 of the LMNA protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a familial case of limb girdle muscular dystrophy (PMID: 22806367). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV004994432	SCV005614275	uncertain significance	Cardiovascular phenotype	2024-11-19	criteria provided, single submitter	clinical testing	The p.A130S variant (also known as c.388G>T), located in coding exon 2 of the LMNA gene, results from a G to T substitution at nucleotide position 388. The alanine at codon 130 is replaced by serine, an amino acid with similar properties. This variant was reported in an individual with features consistent with limb-girdle muscular dystrophy (Carboni N et al. Muscle Nerve, 2012 Aug;46:187-92). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.