Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001731325 | SCV001983589 | uncertain significance | not specified | 2021-09-09 | criteria provided, single submitter | clinical testing | Variant summary: CRLF1 c.242G>A (p.Arg81His) results in a non-conservative amino acid change located in the Ig-like domain (Herholz_2011) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.6e-05 in 232402 control chromosomes (gnomAD and publication data). c.242G>A has been reported in the literature in homozygous state in two individuals (siblings) affected with Cold-Induced Sweating Syndrome. Moreover, another variant (c.1121T>G, p.L374R) was also found in homozygous state in these two siblings (Knappskog_2002). At least one functional study reports experimental evidence evaluating an impact on protein function and this variant altered secretion of the CRLF1 protein (Herholz_2011). One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
Fulgent Genetics, |
RCV000020614 | SCV002803824 | uncertain significance | Cold-induced sweating syndrome 1 | 2022-05-12 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000020614 | SCV000041122 | not provided | Cold-induced sweating syndrome 1 | no assertion provided | literature only | Persons of Israeli ancestry reported as homozygous for both variants c.242G>A and c.1121T>G |