ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.1838G>A (p.Arg613His) (rs147601415)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726099 SCV000341978 uncertain significance not provided 2018-02-28 criteria provided, single submitter clinical testing
GeneDx RCV000726099 SCV000515736 uncertain significance not provided 2018-01-31 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the POMT1 gene. The R635H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R635H variant is observed in 14/126686 (0.01%) alleles from individuals of European background (Lek et al., 2016). The R635H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001070816 SCV001236089 uncertain significance Limb-girdle muscular dystrophy-dystroglycanopathy, type C1; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B1; Walker-Warburg congenital muscular dystrophy 2020-10-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 635 of the POMT1 protein (p.Arg635His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs147601415, ExAC 0.008%). This variant has not been reported in the literature in individuals with POMT1-related disease. ClinVar contains an entry for this variant (Variation ID: 288003). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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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