ClinVar Miner

Submissions for variant NM_004750.5(CRLF1):c.242G>A (p.Arg81His)

gnomAD frequency: 0.00005  dbSNP: rs104894670
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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, Fulgent Genetics RCV000020614 SCV002803824 uncertain significance Cold-induced sweating syndrome 1 2022-05-12 criteria provided, single submitter clinical testing
GeneReviews 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

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