ClinVar Miner

Submissions for variant NM_173660.5(DOK7):c.1133C>T (p.Ala378Val)

gnomAD frequency: 0.00009  dbSNP: rs371846002
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000822754 SCV000963570 uncertain significance Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 10 2022-08-20 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 378 of the DOK7 protein (p.Ala378Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DOK7-related conditions. ClinVar contains an entry for this variant (Variation ID: 664626). 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 tolerated. 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.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV001731945 SCV001984677 likely benign not specified 2020-09-02 criteria provided, single submitter clinical testing
GeneDx RCV001766748 SCV002008747 uncertain significance not provided 2021-11-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); 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; This variant is associated with the following publications: (PMID: 26198629, 20603078, 20012313)
Ambry Genetics RCV003169039 SCV003883936 uncertain significance Inborn genetic diseases 2023-01-06 criteria provided, single submitter clinical testing The c.1133C>T (p.A378V) alteration is located in exon 7 (coding exon 7) of the DOK7 gene. This alteration results from a C to T substitution at nucleotide position 1133, causing the alanine (A) at amino acid position 378 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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