ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1190G>A (p.Arg397His)

gnomAD frequency: 0.00002  dbSNP: rs747952058
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523012 SCV000616766 uncertain significance not provided 2022-06-28 criteria provided, single submitter clinical testing Reported previously in a patient with HCM; however, no further clinical or segregation information was provided. Patient also had a second variant in another gene (Viswanathan et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28663758, 10939567, 29121657)
Labcorp Genetics (formerly Invitae), Labcorp RCV000695647 SCV000824159 likely benign Charcot-Marie-Tooth disease type 2 2024-11-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000523012 SCV001248556 uncertain significance not provided 2019-10-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002341216 SCV002644572 uncertain significance Cardiovascular phenotype 2022-07-21 criteria provided, single submitter clinical testing The p.R397H variant (also known as c.1190G>A), located in coding exon 7 of the LMNA gene, results from a G to A substitution at nucleotide position 1190. The arginine at codon 397 is replaced by histidine, an amino acid with highly similar properties. This variant co-occurred with a pathogenic variant in the MYBPC3 gene in an individual from a hypertrophic cardiomyopathy cohort (Viswanathan SK et al. PLoS One, 2017 Nov;12:e0187948). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV003532151 SCV004359113 uncertain significance Cardiomyopathy 2023-09-07 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 397 of the LMNA protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 29121657); this individual also carried a pathogenic variant in the MYBPC3 gene that could explain the observed phenotype. This variant has been identified in 6/279914 chromosomes 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.
All of Us Research Program, National Institutes of Health RCV004003591 SCV004819594 uncertain significance Primary dilated cardiomyopathy 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 397 of the LMNA protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 29121657); this individual also carried a pathogenic variant in the MYBPC3 gene that could explain the observed phenotype. This variant has been identified in 6/279914 chromosomes 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.
Fulgent Genetics, Fulgent Genetics RCV005044772 SCV005679403 uncertain significance Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome; Dilated cardiomyopathy 1A; Charcot-Marie-Tooth disease type 2B1; Emery-Dreifuss muscular dystrophy 2, autosomal dominant; Heart-hand syndrome, Slovenian type; Hutchinson-Gilford syndrome; Familial partial lipodystrophy, Dunnigan type; Mandibuloacral dysplasia with type A lipodystrophy; Congenital muscular dystrophy due to LMNA mutation; Emery-Dreifuss muscular dystrophy 3, autosomal recessive; Restrictive dermopathy 2 2024-01-31 criteria provided, single submitter clinical testing

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