ClinVar Miner

Submissions for variant NM_138361.5(LRSAM1):c.2120C>T (p.Pro707Leu) (rs797044913)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000190742 SCV000244183 uncertain significance Inborn genetic diseases 2019-11-14 criteria provided, single submitter clinical testing The p.P707L variant (also known as c.2120C>T), located in coding exon 24 of the LRSAM1 gene, results from a C to T substitution at nucleotide position 2120. The proline at codon 707 is replaced by leucine, an amino acid with similar properties. This variant has been reported in one patient with axonal neuropathy affecting both sensory and motor nerves and has been shown to result in an impaired function of the mutant protein (Hakonen JE et al. Hum. Mol. Genet., 2017 06;26:2034-2041). This amino acid position is highly 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.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173632 SCV001336734 likely pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Invitae RCV001224770 SCV001396990 uncertain significance Charcot-Marie-Tooth disease type 2P 2019-06-06 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 707 of the LRSAM1 protein (p.Pro707Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with axonal Charcot-Marie-Tooth disease (PMID: 28335037). ClinVar contains an entry for this variant (Variation ID: 208726). This variant has been reported to affect LRSAM1 protein function (PMID: 28335037). 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.
Institute of Human Genetics, University of Leipzig Medical Center RCV001224770 SCV001428627 likely pathogenic Charcot-Marie-Tooth disease type 2P 2017-05-15 criteria provided, single submitter clinical testing

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