Submissions for variant NM_018947.6(CYCS):c.79C>T (p.His27Tyr)

dbSNP: rs1783403912

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003688943	SCV004434252	pathogenic	not provided	2023-03-03	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 27 of the CYCS protein (p.His27Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with familial thrombocytopenia (PMID: 35126455). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1210164). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001580209	SCV004806952	likely pathogenic	Thrombocytopenia 4	2024-03-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001580209	SCV005062114	pathogenic	Thrombocytopenia 4	2024-03-05	criteria provided, single submitter	clinical testing	Variant summary: CYCS c.79C>T (p.His27Tyr) results in a conservative amino acid change located in the Cytochrome c-like domain (IPR009056) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251314 control chromosomes. c.79C>T has been reported in the literature in multiple individuals from a large family affected with Thrombocytopenia and co-segregated with disease (Che_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 35126455). ClinVar contains an entry for this variant (Variation ID: 1210164). Based on the evidence outlined above, the variant was classified as pathogenic.
Shaanxi Institute for Pediatric Diseases, Xi'an Children's Hospital	RCV001580209	SCV001806776	uncertain significance	Thrombocytopenia 4	2021-08-24	no assertion criteria provided	clinical testing	We described a 3-generation pedigree in which 8 individuals had thrombocytopenia. Affected individuals had platelet counts ranging from 38 to 110×109/L with a reference interval of 100 to 300×109/L. The mean platelet volumes and morphology were normal. Clinical features of thrombocytopenia were mild. None of the individuals had bleeding abnormalities or mitochondriopathies. A novel heterozygous missense variant c.79C>T(p.His27Tyr) of CYCS gene was identified in this family and segregated with autosomal dominant thrombocytopenia.