ClinVar Miner

Submissions for variant NM_170606.3(KMT2C):c.6339A>C (p.Ser2113=)

dbSNP: rs73161892
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000958608 SCV001105473 benign not provided 2024-01-08 criteria provided, single submitter clinical testing
Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino RCV001824394 SCV002074130 pathogenic Tip-toe gait 2021-10-21 criteria provided, single submitter clinical testing Hereditary motor sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth Disease (CMT), is the most commonly inherited peripheral polyneuropathy. It constitutes a group of inherited, progressive, motor and sensory peripheral nerve disorders with properties of demyelination, axonal degeneration, or both. It is classified by clinical characteristics, modes of inheritance, electrophysiologic features, metabolic defects, and specific gene markers. Our patients all walk on tiptoe, so they show similar symptoms. When we genetically test them with our toe walking panel, we find that around 90 per cent of them have a genetic variant that explains their toe walking. These can be assigned, for example, to the area of myopathies (such as variants of the COL6A3 gene), the area of hereditary neuropathies (such as variants of the KMT2C gene) or the area of metabolic diseases (such as variants of the PYGM gene). In a smaller group of patients with almost identical symptoms, no abnormality is found in the genes of our panel, but spastic paraplegia can be detected. In another small group of our toe walkers, no abnormalities can be detected in the genes analysed in our toe walking panel, nor do they suffer from spastic paraplegia, as is also the case with healthy children. In contrast to these, however, they show a tiptoe gait. These patients suffer from infantile cerebral palsy, in which toe walking can also be observed.
CeGaT Center for Human Genetics Tuebingen RCV000958608 SCV004010746 benign not provided 2024-08-01 criteria provided, single submitter clinical testing KMT2C: BP4, BP7, BS1, BS2
Molecular Genetics, Royal Melbourne Hospital RCV003994178 SCV004812451 benign Syndromic intellectual disability 2023-06-06 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017765 SCV004847397 likely benign not specified 2024-01-01 criteria provided, single submitter clinical testing The p.Ser2113Ser variant in KMT2C is classified as likely benign because it has been identified in 1.1% (795/68002) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). In addition it does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact on splicing. ACMG/AMP Criteria applied: BS1, BP7.

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