ClinVar Miner

Submissions for variant NM_144773.4(PROKR2):c.337T>C (p.Tyr113His)

gnomAD frequency: 0.00004  dbSNP: rs202203360
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000404745 SCV000434478 likely benign Hypogonadotropic hypogonadism 3 with or without anosmia 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Mendelics RCV002248622 SCV002519218 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003556350 SCV004284890 likely pathogenic not provided 2023-10-20 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 113 of the PROKR2 protein (p.Tyr113His). This variant is present in population databases (rs202203360, gnomAD 0.2%). This missense change has been observed in individuals with clinical features of Kallmann syndrome (PMID: 18559922, 26031747, 28858133, 30576231, 32400067, 33411215, 34348883, 35090434, 35922219). ClinVar contains an entry for this variant (Variation ID: 338862). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PROKR2 protein function. Experimental studies have shown that this missense change affects PROKR2 function (PMID: 18559922, 24830383, 29161432). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000404745 SCV005660829 uncertain significance Hypogonadotropic hypogonadism 3 with or without anosmia 2024-05-16 criteria provided, single submitter clinical testing

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