ClinVar Miner

Submissions for variant NM_000751.3(CHRND):c.919C>T (p.Pro307Ser) (rs142063328)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724895 SCV000332203 uncertain significance not provided 2017-03-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764381 SCV000895433 uncertain significance Lethal multiple pterygium syndrome; Myasthenic syndrome, congenital, 3a, slow-channel; Myasthenic syndrome, congenital, 3b, fast-channel; Myasthenic syndrome, congenital, 3c, associated with acetylcholine receptor deficiency 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000724895 SCV000570739 uncertain significance not provided 2016-06-20 criteria provided, single submitter clinical testing The P307S variant in the CHRND gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports P307S was observed in 10/8600 alleles from individuals of European American background, indicating it may be a rare variant in this population. The P307S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P307S as a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000289236 SCV000428419 uncertain significance Congenital Myasthenic Syndrome, Dominant/Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000346718 SCV000428420 uncertain significance Multiple pterygium syndrome Escobar type 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000551903 SCV000641739 uncertain significance Lethal multiple pterygium syndrome 2018-05-29 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 307 of the CHRND protein (p.Pro307Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs142063328, ExAC 0.1%) but has not been reported in the literature in individuals with a CHRND-related disease. ClinVar contains an entry for this variant (Variation ID: 281423). 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. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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