TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2709	8350;8351;8352	chr2:178770667;178770666;178770665	chr2:179635394;179635393;179635392
N2AB	2709	8350;8351;8352	chr2:178770667;178770666;178770665	chr2:179635394;179635393;179635392
N2A	2709	8350;8351;8352	chr2:178770667;178770666;178770665	chr2:179635394;179635393;179635392
N2B	2663	8212;8213;8214	chr2:178770667;178770666;178770665	chr2:179635394;179635393;179635392
Novex-1	2663	8212;8213;8214	chr2:178770667;178770666;178770665	chr2:179635394;179635393;179635392
Novex-2	2663	8212;8213;8214	chr2:178770667;178770666;178770665	chr2:179635394;179635393;179635392
Novex-3	2709	8350;8351;8352	chr2:178770667;178770666;178770665	chr2:179635394;179635393;179635392

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-17
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1265
• 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
I/S	rs2091328773	None	0.991	D	0.797	0.716	0.854516633281	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
I/S	rs2091328773	None	0.991	D	0.797	0.716	0.854516633281	gnomAD-4.0.0	6.56978E-06	None	None	None	None	N	None	0	6.5445E-05	None	0	0	None	0	0	0	0	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
I/A	0.8579	likely_pathogenic	0.9443	pathogenic	-1.871	Destabilizing	0.91	D	0.628	neutral	None	None	None	None	N
I/C	0.9141	likely_pathogenic	0.9611	pathogenic	-1.253	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
I/D	0.9745	likely_pathogenic	0.9928	pathogenic	-1.233	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
I/E	0.9285	likely_pathogenic	0.9774	pathogenic	-1.133	Destabilizing	0.993	D	0.836	deleterious	None	None	None	None	N
I/F	0.3148	likely_benign	0.421	ambiguous	-1.029	Destabilizing	0.982	D	0.698	prob.neutral	N	0.493596821	None	None	N
I/G	0.9447	likely_pathogenic	0.9799	pathogenic	-2.302	Highly Destabilizing	0.993	D	0.825	deleterious	None	None	None	None	N
I/H	0.9285	likely_pathogenic	0.9756	pathogenic	-1.485	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
I/K	0.8789	likely_pathogenic	0.9563	pathogenic	-1.408	Destabilizing	0.993	D	0.837	deleterious	None	None	None	None	N
I/L	0.1988	likely_benign	0.2422	benign	-0.71	Destabilizing	0.58	D	0.499	neutral	N	0.518343889	None	None	N
I/M	0.1635	likely_benign	0.2097	benign	-0.647	Destabilizing	0.991	D	0.661	neutral	D	0.646050176	None	None	N
I/N	0.7794	likely_pathogenic	0.9147	pathogenic	-1.382	Destabilizing	0.997	D	0.835	deleterious	D	0.64919443	None	None	N
I/P	0.8958	likely_pathogenic	0.9544	pathogenic	-1.068	Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	N
I/Q	0.8778	likely_pathogenic	0.9565	pathogenic	-1.399	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
I/R	0.8322	likely_pathogenic	0.9366	pathogenic	-0.962	Destabilizing	0.993	D	0.841	deleterious	None	None	None	None	N
I/S	0.8527	likely_pathogenic	0.9488	pathogenic	-2.108	Highly Destabilizing	0.991	D	0.797	deleterious	D	0.648367825	None	None	N
I/T	0.8453	likely_pathogenic	0.942	pathogenic	-1.871	Destabilizing	0.939	D	0.725	prob.delet.	D	0.647892974	None	None	N
I/V	0.1329	likely_benign	0.1764	benign	-1.068	Destabilizing	0.02	N	0.283	neutral	N	0.50872146	None	None	N
I/W	0.8896	likely_pathogenic	0.9447	pathogenic	-1.188	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
I/Y	0.7409	likely_pathogenic	0.8586	pathogenic	-0.95	Destabilizing	0.993	D	0.714	prob.delet.	None	None	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.