Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001957279 | SCV002199411 | likely benign | Charcot-Marie-Tooth disease axonal type 2O | 2023-10-11 | criteria provided, single submitter | clinical testing | |
Diagnostic Genetics, |
RCV002466275 | SCV002761276 | likely pathogenic | Intellectual disability, autosomal dominant 13 | 2022-02-03 | criteria provided, single submitter | clinical testing | |
Department of Genetics, |
RCV003126001 | SCV003803820 | uncertain significance | Autism spectrum disorder | criteria provided, single submitter | clinical testing | ||
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004587257 | SCV005076919 | uncertain significance | not specified | 2024-04-08 | criteria provided, single submitter | clinical testing | Variant summary: DYNC1H1 c.12419G>A (p.Arg4140His) results in a non-conservative amino acid change located in the dynein heavy chain region D6 P-loop domain (IPR004273) of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251374 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.12419G>A has been reported in the literature in at least one individuals affected with clinical features of DYNC1H1-Related Disorders (e.g., Volodarsky_2021). However, these report(s) do not provide unequivocal conclusions about association of the variant with DYNC1H1-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 1424891). Based on the evidence outlined above, the variant was classified as uncertain significance. |