ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1931G>A (p.Arg644His)

gnomAD frequency: 0.00004  dbSNP: rs368386019
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001079490 SCV000291557 likely benign Charcot-Marie-Tooth disease type 2 2024-01-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000245708 SCV000320352 uncertain significance Cardiovascular phenotype 2022-09-01 criteria provided, single submitter clinical testing The p.R644H variant (also known as c.1931G>A), located in coding exon 11 of the LMNA gene, results from a G to A substitution at nucleotide position 1931. The arginine at codon 644 is replaced by histidine, an amino acid with highly similar properties. This variant previously was described in a case report involving an infant with persistent failure to thrive, delayed motor development, skeletal abnormalities, muscle weakness and wasting, elevated CK levels, and myopathic EMG (Mercuri E et al. Muscle Nerve. 2005;31(5):602-9). Using alternate nomenclature, this variant (p.R532H c.1595G>A) has also been seen in an exome cohort, but cardiovascular history was not provided (Amendola LM et al. Genome Res. 2015;25(3):305-15). Limited functional studies suggested normal localization to the nuclear membrane and no prelamin A accumulation in mouse fibroblasts with this alteration (Casasola A et al. Nucleus, 2016;7:84-102). This amino acid position is well conserved in available vertebrates; however, histidine is the reference amino acid in other 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 variant remains unclear.
Eurofins Ntd Llc (ga) RCV000725647 SCV000338355 uncertain significance not provided 2015-12-11 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000182377 SCV000614027 uncertain significance not specified 2017-03-30 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769735 SCV000901157 uncertain significance Cardiomyopathy 2017-08-04 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000769735 SCV000913870 likely benign Cardiomyopathy 2018-10-30 criteria provided, single submitter clinical testing
Baylor Genetics RCV001330501 SCV001522192 uncertain significance Lethal tight skin contracture syndrome 2019-06-07 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Revvity Omics, Revvity Omics RCV000725647 SCV003814729 uncertain significance not provided 2019-10-14 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148599 SCV000190314 likely benign Congenital muscular dystrophy 2014-06-01 no assertion criteria provided research
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000725647 SCV002036340 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000725647 SCV002037670 uncertain significance not provided no assertion criteria provided clinical testing

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