Submissions for variant NM_024753.5(TTC21B):c.3664C>T (p.Arg1222Trp)

gnomAD frequency: 0.00003  dbSNP: rs749330118

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Precision Medicine Center, Zhengzhou University	RCV001391113	SCV001593016	likely pathogenic	Nephronophthisis 12		criteria provided, single submitter	research	PM2:not found in gnomAD PP1:Cosegregation with disease in multiple affected family members PP3:Multiple lines of computational evidence support a deleterious effect on the gene or gene product PP4:Patient's phenotype is highly specific for a disease PP5:Reputable source recently reports variant as pathogenic
PreventionGenetics, part of Exact Sciences	RCV004734166	SCV005348213	uncertain significance	TTC21B-related disorder	2024-07-17	no assertion criteria provided	clinical testing	The TTC21B c.3664C>T variant is predicted to result in the amino acid substitution p.Arg1222Trp. This variant was reported in the compound heterozygous state with a likely benign variant, defined as c.256A>C (p.Asn86His), in an individual with focal segmental glomerulosclerosis (FSGS) (Table 1 of Wang et al. 2021. PubMed ID: 34215756). This variant is reported in 0.0085% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.