ClinVar Miner

Submissions for variant NM_022773.4(LMF1):c.383T>A (p.Leu128Ter)

dbSNP: rs2072617381
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003165017 SCV003860924 uncertain significance Cardiovascular phenotype 2023-03-07 criteria provided, single submitter clinical testing The p.L128* variant (also known as c.383T>A), located in coding exon 2 of the LMF1 gene, results from a T to A substitution at nucleotide position 383. This changes the amino acid from a leucine to a stop codon within coding exon 2. This alteration has been reported as a heterozygote in both congenital heart disease and chylomicromemia syndrome cohorts (Jin SC et al. Nat Genet, 2017 Nov;49:1593-1601; D'Erasmo L et al. Arterioscler Thromb Vasc Biol, 2019 Dec;39:2531-2541). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, this region of the LMF1 gene is excluded from other biologically relevant LMF1 transcripts. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003396930 SCV004104826 likely pathogenic LMF1-related disorder 2022-09-22 criteria provided, single submitter clinical testing The LMF1 c.383T>A variant is predicted to result in premature protein termination (p.Leu128*). This variant has been reported in a cohort study with Chylomicronemia syndrome (D'Erasmo et al. 2019. PubMed ID: 31619059. Table S2). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in LMF1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003778937 SCV004630859 pathogenic not provided 2023-08-22 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2447059). This premature translational stop signal has been observed in individual(s) with chylomicronemia syndrome (PMID: 31619059). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu128*) in the LMF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LMF1 are known to be pathogenic (PMID: 17994020, 19820022, 22239554).

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