ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1044G>T (p.Met348Ile)

gnomAD frequency: 0.00001  dbSNP: rs587777892
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001243750 SCV001416931 uncertain significance Charcot-Marie-Tooth disease type 2 2022-12-22 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change does not substantially affect LMNA function (PMID: 34862408). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LMNA protein function. ClinVar contains an entry for this variant (Variation ID: 155896). This missense change has been observed in individual(s) with clinical features of LMNA-related conditions (PMID: 22103509, 27405450). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 348 of the LMNA protein (p.Met348Ile).
Fulgent Genetics, Fulgent Genetics RCV002483277 SCV002794165 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 2021-12-17 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998157 SCV004815940 uncertain significance Primary dilated cardiomyopathy 2023-02-24 criteria provided, single submitter clinical testing This missense variant replaces methionine with isoleucine at codon 348 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 arrhythmogenic right ventricular cardiomyopathy (PMID: 27405450) and in an individual affected with Emery-Dreyfuss muscular dystrophy and dilated cardiomyopathy (PMID: 22103509). 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.
SNPedia RCV000144027 SCV000188920 not provided not provided no assertion provided not provided

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