TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22138	66637;66638;66639	chr2:178581957;178581956;178581955	chr2:179446684;179446683;179446682
N2AB	20497	61714;61715;61716	chr2:178581957;178581956;178581955	chr2:179446684;179446683;179446682
N2A	19570	58933;58934;58935	chr2:178581957;178581956;178581955	chr2:179446684;179446683;179446682
N2B	13073	39442;39443;39444	chr2:178581957;178581956;178581955	chr2:179446684;179446683;179446682
Novex-1	13198	39817;39818;39819	chr2:178581957;178581956;178581955	chr2:179446684;179446683;179446682
Novex-2	13265	40018;40019;40020	chr2:178581957;178581956;178581955	chr2:179446684;179446683;179446682
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: Fn3-48
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.4908
• 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/S	rs759290401	-0.736	0.946	N	0.717	0.256	0.286848849266	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
P/S	rs759290401	-0.736	0.946	N	0.717	0.256	0.286848849266	gnomAD-4.0.0	1.59249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86035E-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	0.0638	likely_benign	0.0646	benign	-0.975	Destabilizing	0.896	D	0.659	neutral	N	0.45338996	None	None	N
P/C	0.3357	likely_benign	0.343	ambiguous	-0.7	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
P/D	0.5828	likely_pathogenic	0.5313	ambiguous	-0.687	Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	N
P/E	0.3188	likely_benign	0.2749	benign	-0.775	Destabilizing	0.996	D	0.741	deleterious	None	None	None	None	N
P/F	0.3001	likely_benign	0.2863	benign	-1.002	Destabilizing	0.976	D	0.814	deleterious	None	None	None	None	N
P/G	0.3346	likely_benign	0.3265	benign	-1.179	Destabilizing	0.996	D	0.781	deleterious	None	None	None	None	N
P/H	0.2129	likely_benign	0.1777	benign	-0.685	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
P/I	0.1444	likely_benign	0.1391	benign	-0.562	Destabilizing	0.851	D	0.745	deleterious	None	None	None	None	N
P/K	0.3696	ambiguous	0.2868	benign	-0.767	Destabilizing	0.988	D	0.727	prob.delet.	None	None	None	None	N
P/L	0.0769	likely_benign	0.0799	benign	-0.562	Destabilizing	0.011	N	0.561	neutral	N	0.397998037	None	None	N
P/M	0.167	likely_benign	0.1636	benign	-0.417	Destabilizing	0.976	D	0.818	deleterious	None	None	None	None	N
P/N	0.3015	likely_benign	0.2966	benign	-0.446	Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
P/Q	0.1576	likely_benign	0.1432	benign	-0.718	Destabilizing	0.995	D	0.763	deleterious	N	0.448002783	None	None	N
P/R	0.2711	likely_benign	0.2024	benign	-0.175	Destabilizing	0.984	D	0.82	deleterious	N	0.461452083	None	None	N
P/S	0.1331	likely_benign	0.1301	benign	-0.877	Destabilizing	0.946	D	0.717	prob.delet.	N	0.452216524	None	None	N
P/T	0.092	likely_benign	0.0848	benign	-0.863	Destabilizing	0.946	D	0.713	prob.delet.	N	0.452851243	None	None	N
P/V	0.1088	likely_benign	0.1072	benign	-0.663	Destabilizing	0.851	D	0.727	prob.delet.	None	None	None	None	N
P/W	0.5702	likely_pathogenic	0.5054	ambiguous	-1.072	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
P/Y	0.3533	ambiguous	0.3211	benign	-0.795	Destabilizing	0.988	D	0.818	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.