TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28157	84694;84695;84696	chr2:178561663;178561662;178561661	chr2:179426390;179426389;179426388
N2AB	26516	79771;79772;79773	chr2:178561663;178561662;178561661	chr2:179426390;179426389;179426388
N2A	25589	76990;76991;76992	chr2:178561663;178561662;178561661	chr2:179426390;179426389;179426388
N2B	19092	57499;57500;57501	chr2:178561663;178561662;178561661	chr2:179426390;179426389;179426388
Novex-1	19217	57874;57875;57876	chr2:178561663;178561662;178561661	chr2:179426390;179426389;179426388
Novex-2	19284	58075;58076;58077	chr2:178561663;178561662;178561661	chr2:179426390;179426389;179426388
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-93
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3511
• Predicted PPI site: I

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
P/L	None	None	0.988	D	0.87	0.516	0.740553466771	gnomAD-4.0.0	1.60947E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.45366E-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
P/A	0.1438	likely_benign	0.1292	benign	-1.26	Destabilizing	0.958	D	0.797	deleterious	N	0.480939134	None	None	I
P/C	0.6929	likely_pathogenic	0.6303	pathogenic	-0.898	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	I
P/D	0.9503	likely_pathogenic	0.918	pathogenic	-1.203	Destabilizing	0.995	D	0.843	deleterious	None	None	None	None	I
P/E	0.7479	likely_pathogenic	0.6628	pathogenic	-1.272	Destabilizing	0.991	D	0.827	deleterious	None	None	None	None	I
P/F	0.7473	likely_pathogenic	0.6897	pathogenic	-1.247	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	I
P/G	0.7668	likely_pathogenic	0.7216	pathogenic	-1.494	Destabilizing	0.991	D	0.833	deleterious	None	None	None	None	I
P/H	0.574	likely_pathogenic	0.5019	ambiguous	-1.019	Destabilizing	0.998	D	0.897	deleterious	D	0.531307545	None	None	I
P/I	0.5386	ambiguous	0.4948	ambiguous	-0.746	Destabilizing	0.995	D	0.896	deleterious	None	None	None	None	I
P/K	0.7769	likely_pathogenic	0.7376	pathogenic	-0.938	Destabilizing	0.938	D	0.813	deleterious	None	None	None	None	I
P/L	0.322	likely_benign	0.2924	benign	-0.746	Destabilizing	0.988	D	0.87	deleterious	D	0.531054055	None	None	I
P/M	0.5171	ambiguous	0.4697	ambiguous	-0.518	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
P/N	0.8119	likely_pathogenic	0.7215	pathogenic	-0.649	Destabilizing	0.991	D	0.87	deleterious	None	None	None	None	I
P/Q	0.445	ambiguous	0.3896	ambiguous	-0.948	Destabilizing	0.991	D	0.856	deleterious	None	None	None	None	I
P/R	0.637	likely_pathogenic	0.5804	pathogenic	-0.362	Destabilizing	0.142	N	0.645	neutral	N	0.500326047	None	None	I
P/S	0.3432	ambiguous	0.2679	benign	-1.095	Destabilizing	0.988	D	0.828	deleterious	N	0.482284244	None	None	I
P/T	0.3599	ambiguous	0.3031	benign	-1.067	Destabilizing	0.988	D	0.817	deleterious	N	0.496313576	None	None	I
P/V	0.4201	ambiguous	0.3865	ambiguous	-0.883	Destabilizing	0.995	D	0.871	deleterious	None	None	None	None	I
P/W	0.9247	likely_pathogenic	0.9035	pathogenic	-1.321	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
P/Y	0.7956	likely_pathogenic	0.7461	pathogenic	-1.04	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	I

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.