ClinVar Miner

Submissions for variant NM_006158.5(NEFL):c.64C>T (p.Pro22Ser) (rs28928910)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415401 SCV000493018 likely pathogenic Pes cavus; Distal lower limb muscle weakness; Peripheral neuropathy 2014-06-03 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414916 SCV000493036 pathogenic Decreased nerve conduction velocity; Distal muscle weakness; Hand muscle atrophy; Peripheral demyelination; Peripheral neuropathy 2014-06-11 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196666 SCV001367296 likely pathogenic Pes cavus; Distal lower limb muscle weakness; Clubbing of toes; Peripheral neuropathy 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. This variant was detected in heterozygous state.
Invitae RCV000015073 SCV001377432 pathogenic Charcot-Marie-Tooth disease type 2E 2019-09-23 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 22 of the NEFL protein (p.Pro22Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (rs28928910, ExAC no frequency). This sequence change has been reported in the heterozygous state in individuals affected with mixed axonal and demyelinating neuropathy (PMID: 15111691, 19286384). This variant has been reported to segregate with autosomal dominant Charcot-Marie-Tooth disease in several families (PMID: 12481988, 15111691). ClinVar contains an entry for this variant (Variation ID: 14029). Experimental studies have shown that this missense change disrupts the function of the NEFL protein (PMID: 21168446, 16452125). For these reasons, this sequence change has been classified as Pathogenic.
OMIM RCV000015073 SCV000035329 pathogenic Charcot-Marie-Tooth disease type 2E 2006-03-15 no assertion criteria provided literature only
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057144 SCV000088257 not provided not provided no assertion provided not provided
GeneReviews RCV000194357 SCV000243953 pathogenic Charcot-Marie-Tooth disease, type 1C 2014-12-18 no assertion criteria provided literature only

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