ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.1523C>T (p.Ser508Leu) (rs754465226)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children RCV000498809 SCV000590850 uncertain significance not specified 2017-01-05 criteria provided, single submitter clinical testing
Invitae RCV001068853 SCV001233986 uncertain significance Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 508 of the IGHMBP2 protein (p.Ser508Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs754465226, ExAC 0.004%). This variant has been observed in individuals with clinical features of Charcot-Marie-Tooth disease (PMID: 29858556, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 433162). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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,Cologne University RCV000664228 SCV000787793 likely pathogenic Charcot-Marie-Tooth disease, axonal, type 2S 2018-04-25 no assertion criteria provided clinical testing
Genesis Genome Database RCV000856971 SCV000999537 uncertain significance Charcot-Marie-Tooth disease 2019-08-14 no assertion criteria provided research

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