TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15445	46558;46559;46560	chr2:178620084;178620083;178620082	chr2:179484811;179484810;179484809
N2AB	13804	41635;41636;41637	chr2:178620084;178620083;178620082	chr2:179484811;179484810;179484809
N2A	12877	38854;38855;38856	chr2:178620084;178620083;178620082	chr2:179484811;179484810;179484809
N2B	6380	19363;19364;19365	chr2:178620084;178620083;178620082	chr2:179484811;179484810;179484809
Novex-1	6505	19738;19739;19740	chr2:178620084;178620083;178620082	chr2:179484811;179484810;179484809
Novex-2	6572	19939;19940;19941	chr2:178620084;178620083;178620082	chr2:179484811;179484810;179484809
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-106
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1986
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
H/R	None	None	0.896	N	0.729	0.292	0.349429436713	gnomAD-4.0.0	1.59675E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86651E-06	0	0
H/Y	rs1295193843	0.389	0.004	N	0.408	0.177	0.273938319068	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.3E-05	None	0	0	0
H/Y	rs1295193843	0.389	0.004	N	0.408	0.177	0.273938319068	gnomAD-4.0.0	1.59686E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4415E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
H/A	0.7297	likely_pathogenic	0.8539	pathogenic	-1.663	Destabilizing	0.4	N	0.745	deleterious	None	None	None	None	N
H/C	0.2157	likely_benign	0.3165	benign	-0.911	Destabilizing	0.002	N	0.623	neutral	None	None	None	None	N
H/D	0.8997	likely_pathogenic	0.9479	pathogenic	-1.606	Destabilizing	0.883	D	0.732	prob.delet.	D	0.534028764	None	None	N
H/E	0.874	likely_pathogenic	0.9232	pathogenic	-1.417	Destabilizing	0.766	D	0.694	prob.neutral	None	None	None	None	N
H/F	0.4673	ambiguous	0.5999	pathogenic	0.262	Stabilizing	0.447	N	0.716	prob.delet.	None	None	None	None	N
H/G	0.8346	likely_pathogenic	0.9187	pathogenic	-2.077	Highly Destabilizing	0.766	D	0.742	deleterious	None	None	None	None	N
H/I	0.7051	likely_pathogenic	0.819	pathogenic	-0.443	Destabilizing	0.617	D	0.783	deleterious	None	None	None	None	N
H/K	0.8302	likely_pathogenic	0.865	pathogenic	-1.091	Destabilizing	0.617	D	0.72	prob.delet.	None	None	None	None	N
H/L	0.3662	ambiguous	0.4621	ambiguous	-0.443	Destabilizing	0.379	N	0.745	deleterious	N	0.508453055	None	None	N
H/M	0.7831	likely_pathogenic	0.873	pathogenic	-0.687	Destabilizing	0.972	D	0.737	prob.delet.	None	None	None	None	N
H/N	0.361	ambiguous	0.5091	ambiguous	-1.679	Destabilizing	0.712	D	0.69	prob.neutral	D	0.534528706	None	None	N
H/P	0.9246	likely_pathogenic	0.9512	pathogenic	-0.84	Destabilizing	0.963	D	0.755	deleterious	D	0.591865933	None	None	N
H/Q	0.5349	ambiguous	0.6491	pathogenic	-1.267	Destabilizing	0.896	D	0.735	prob.delet.	N	0.51014321	None	None	N
H/R	0.5025	ambiguous	0.507	ambiguous	-1.342	Destabilizing	0.896	D	0.729	prob.delet.	N	0.485783339	None	None	N
H/S	0.5602	ambiguous	0.73	pathogenic	-1.803	Destabilizing	0.617	D	0.727	prob.delet.	None	None	None	None	N
H/T	0.6784	likely_pathogenic	0.8475	pathogenic	-1.501	Destabilizing	0.766	D	0.739	prob.delet.	None	None	None	None	N
H/V	0.5958	likely_pathogenic	0.7395	pathogenic	-0.84	Destabilizing	0.617	D	0.765	deleterious	None	None	None	None	N
H/W	0.5761	likely_pathogenic	0.6473	pathogenic	0.786	Stabilizing	0.977	D	0.732	prob.delet.	None	None	None	None	N
H/Y	0.146	likely_benign	0.2021	benign	0.611	Stabilizing	0.004	N	0.408	neutral	N	0.503234198	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.