TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26684	80275;80276;80277	chr2:178566082;178566081;178566080	chr2:179430809;179430808;179430807
N2AB	25043	75352;75353;75354	chr2:178566082;178566081;178566080	chr2:179430809;179430808;179430807
N2A	24116	72571;72572;72573	chr2:178566082;178566081;178566080	chr2:179430809;179430808;179430807
N2B	17619	53080;53081;53082	chr2:178566082;178566081;178566080	chr2:179430809;179430808;179430807
Novex-1	17744	53455;53456;53457	chr2:178566082;178566081;178566080	chr2:179430809;179430808;179430807
Novex-2	17811	53656;53657;53658	chr2:178566082;178566081;178566080	chr2:179430809;179430808;179430807
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-82
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1279
• 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
P/A	rs1705731534	None	1.0	D	0.82	0.717	0.716839308784	gnomAD-4.0.0	2.05278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69861E-06	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
P/A	0.8801	likely_pathogenic	0.8547	pathogenic	-1.459	Destabilizing	1.0	D	0.82	deleterious	D	0.642343753	None	None	N
P/C	0.9912	likely_pathogenic	0.9919	pathogenic	-1.82	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.108	Highly Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/E	0.9992	likely_pathogenic	0.999	pathogenic	-3.067	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9997	pathogenic	-1.135	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/G	0.9964	likely_pathogenic	0.9959	pathogenic	-1.762	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/H	0.9988	likely_pathogenic	0.9987	pathogenic	-1.179	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
P/I	0.9949	likely_pathogenic	0.9946	pathogenic	-0.692	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
P/K	0.9994	likely_pathogenic	0.9994	pathogenic	-1.37	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/L	0.9814	likely_pathogenic	0.9787	pathogenic	-0.692	Destabilizing	1.0	D	0.822	deleterious	D	0.654587758	None	None	N
P/M	0.9971	likely_pathogenic	0.997	pathogenic	-0.882	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/N	0.9995	likely_pathogenic	0.9995	pathogenic	-1.629	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/Q	0.9982	likely_pathogenic	0.9979	pathogenic	-1.833	Destabilizing	1.0	D	0.82	deleterious	D	0.680327674	None	None	N
P/R	0.9971	likely_pathogenic	0.9968	pathogenic	-0.875	Destabilizing	1.0	D	0.822	deleterious	D	0.68012587	None	None	N
P/S	0.9854	likely_pathogenic	0.9836	pathogenic	-1.945	Destabilizing	1.0	D	0.759	deleterious	D	0.679924066	None	None	N
P/T	0.9834	likely_pathogenic	0.9797	pathogenic	-1.806	Destabilizing	1.0	D	0.765	deleterious	D	0.68012587	None	None	N
P/V	0.9803	likely_pathogenic	0.9786	pathogenic	-0.919	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.43	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9997	pathogenic	-1.082	Destabilizing	1.0	D	0.815	deleterious	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.