TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28487	85684;85685;85686	chr2:178560673;178560672;178560671	chr2:179425400;179425399;179425398
N2AB	26846	80761;80762;80763	chr2:178560673;178560672;178560671	chr2:179425400;179425399;179425398
N2A	25919	77980;77981;77982	chr2:178560673;178560672;178560671	chr2:179425400;179425399;179425398
N2B	19422	58489;58490;58491	chr2:178560673;178560672;178560671	chr2:179425400;179425399;179425398
Novex-1	19547	58864;58865;58866	chr2:178560673;178560672;178560671	chr2:179425400;179425399;179425398
Novex-2	19614	59065;59066;59067	chr2:178560673;178560672;178560671	chr2:179425400;179425399;179425398
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-95
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.1735
• 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/V	rs375122794	None	0.006	N	0.28	0.035	0.527809512145	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.4133	ambiguous	0.3759	ambiguous	-2.497	Highly Destabilizing	0.754	D	0.592	neutral	None	None	None	None	N
I/C	0.7362	likely_pathogenic	0.726	pathogenic	-1.648	Destabilizing	0.994	D	0.696	prob.neutral	None	None	None	None	N
I/D	0.8728	likely_pathogenic	0.8634	pathogenic	-2.846	Highly Destabilizing	0.993	D	0.757	deleterious	None	None	None	None	N
I/E	0.6968	likely_pathogenic	0.6849	pathogenic	-2.629	Highly Destabilizing	0.978	D	0.727	prob.delet.	None	None	None	None	N
I/F	0.2509	likely_benign	0.2256	benign	-1.504	Destabilizing	0.942	D	0.656	neutral	N	0.470279148	None	None	N
I/G	0.8427	likely_pathogenic	0.8215	pathogenic	-3.017	Highly Destabilizing	0.978	D	0.725	prob.delet.	None	None	None	None	N
I/H	0.5794	likely_pathogenic	0.5459	ambiguous	-2.487	Highly Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
I/K	0.3595	ambiguous	0.3504	ambiguous	-1.953	Destabilizing	0.978	D	0.729	prob.delet.	None	None	None	None	N
I/L	0.1542	likely_benign	0.128	benign	-0.999	Destabilizing	0.294	N	0.479	neutral	N	0.511110112	None	None	N
I/M	0.1319	likely_benign	0.1187	benign	-0.904	Destabilizing	0.976	D	0.661	neutral	N	0.49227097	None	None	N
I/N	0.4731	ambiguous	0.4629	ambiguous	-2.286	Highly Destabilizing	0.99	D	0.775	deleterious	N	0.511840831	None	None	N
I/P	0.9762	likely_pathogenic	0.9756	pathogenic	-1.48	Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	N
I/Q	0.5277	ambiguous	0.5014	ambiguous	-2.16	Highly Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	N
I/R	0.2528	likely_benign	0.2435	benign	-1.625	Destabilizing	0.978	D	0.773	deleterious	None	None	None	None	N
I/S	0.4126	ambiguous	0.3959	ambiguous	-2.932	Highly Destabilizing	0.942	D	0.641	neutral	N	0.470528956	None	None	N
I/T	0.1563	likely_benign	0.158	benign	-2.582	Highly Destabilizing	0.822	D	0.61	neutral	N	0.470359568	None	None	N
I/V	0.0715	likely_benign	0.0761	benign	-1.48	Destabilizing	0.006	N	0.28	neutral	N	0.434150839	None	None	N
I/W	0.8435	likely_pathogenic	0.7942	pathogenic	-1.932	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
I/Y	0.5781	likely_pathogenic	0.5393	ambiguous	-1.631	Destabilizing	0.978	D	0.691	prob.neutral	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.