ClinVar Miner

Submissions for variant NM_001243766.1(POMGNT1):c.385C>T (p.Arg129Trp) (rs375431575)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674794 SCV000800192 uncertain significance Muscle eye brain disease 2018-05-24 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001099667 SCV001256139 uncertain significance Congenital Muscular Dystrophy, alpha-dystroglycan related 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001099668 SCV001256140 uncertain significance Limb-girdle muscular dystrophy-dystroglycanopathy, type C3 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001200334 SCV001371263 pathogenic not provided 2020-04-01 criteria provided, single submitter clinical testing
Invitae RCV001244825 SCV001418070 uncertain significance Limb-girdle muscular dystrophy-dystroglycanopathy, type C3; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B3 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 129 of the POMGNT1 protein (p.Arg129Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs375431575, ExAC 0.005%). This variant has been observed in individual(s) with muscular dystrophy-dystroglycanopathy (PMID: 30961548, 28688748). 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: 558512). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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