ClinVar Miner

Submissions for variant NM_133642.5(LARGE1):c.1892C>T (p.Thr631Met)

gnomAD frequency: 0.00016  dbSNP: rs368043810
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000814080 SCV000954477 uncertain significance Muscular dystrophy-dystroglycanopathy type B6 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 631 of the LARGE1 protein (p.Thr631Met). This variant is present in population databases (rs368043810, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LARGE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 657473). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LARGE1 protein function. 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.
GeneDx RCV001786418 SCV002028868 likely benign not provided 2021-04-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002539943 SCV003677201 uncertain significance Inborn genetic diseases 2022-07-08 criteria provided, single submitter clinical testing The c.1892C>T (p.T631M) alteration is located in exon 15 (coding exon 13) of the LARGE1 gene. This alteration results from a C to T substitution at nucleotide position 1892, causing the threonine (T) at amino acid position 631 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001786418 SCV003816471 uncertain significance not provided 2021-02-04 criteria provided, single submitter clinical testing

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