ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1912G>A (p.Gly638Arg) (rs144851946)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041338 SCV000065031 likely benign not specified 2012-08-14 criteria provided, single submitter clinical testing Gly638Arg in exon 11 of LMNA: This variant is not expected to have clinical sign ificance because it has been identified in 0.3% (12/4406) African American chrom osomes from a broad population by the NHLBI Exome Sequencing Project (http://evs .gs.washington.edu/EVS; dbSNP rs144851946). Gly638Arg in exon 11 of LMNA (rs144 851946; allele frequency = 0.3%, 12/4406) **
GeneDx RCV000725381 SCV000234712 uncertain significance not provided 2018-05-03 criteria provided, single submitter clinical testing The G638R variant has been reported previously in association with cardiolaminopathy, however, clinical and segregation information was not provided in these publications (Narula et al., 2012; van Rijsingen et al., 2013). In addition, G638R was identified in one Caucasian male and one African American female with DCM, though the variant was classified as likely benign due to the minor allele frequency exceeding set thresholds determined by the authors (Pugh et al., 2014). Similarly, the G638R variant is observed in48/23736 (0.1%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016). Nonetheless, the G638R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, this substitution occurs at a position that is conserved in mammals. Finally, in silico analysis is inconsistent in its prediction as to whether or not this variant is damaging to the protein structure/function.
Invitae RCV001084443 SCV000291556 likely benign Charcot-Marie-Tooth disease, type 2 2019-12-31 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725381 SCV000336486 uncertain significance not provided 2017-11-10 criteria provided, single submitter clinical testing
Color RCV001188113 SCV001355085 likely benign Cardiomyopathy 2018-12-02 criteria provided, single submitter clinical testing

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