ClinVar Miner

Submissions for variant NM_014112.5(TRPS1):c.3698G>A (p.Cys1233Tyr)

dbSNP: rs1586249260
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002535737 SCV003315081 likely pathogenic Trichorhinophalangeal syndrome, type III; Trichorhinophalangeal dysplasia type I 2023-03-23 criteria provided, single submitter clinical testing 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. This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1233 of the TRPS1 protein (p.Cys1233Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with trichorhinophalangeal syndrome (PMID: 31884116; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 635360). 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 TRPS1 protein function. This variant disrupts the p.Cys1233 amino acid residue in TRPS1. Other variant(s) that disrupt this residue have been observed in individuals with TRPS1-related conditions (PMID: 24357341), which suggests that this may be a clinically significant amino acid residue.
Clinical Genomics Unit, Sheba Medical Center RCV000786782 SCV000925600 pathogenic Trichorhinophalangeal dysplasia type I no assertion criteria provided clinical testing

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