TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16188	48787;48788;48789	chr2:178615383;178615382;178615381	chr2:179480110;179480109;179480108
N2AB	14547	43864;43865;43866	chr2:178615383;178615382;178615381	chr2:179480110;179480109;179480108
N2A	13620	41083;41084;41085	chr2:178615383;178615382;178615381	chr2:179480110;179480109;179480108
N2B	7123	21592;21593;21594	chr2:178615383;178615382;178615381	chr2:179480110;179480109;179480108
Novex-1	7248	21967;21968;21969	chr2:178615383;178615382;178615381	chr2:179480110;179480109;179480108
Novex-2	7315	22168;22169;22170	chr2:178615383;178615382;178615381	chr2:179480110;179480109;179480108
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-5
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.641
• 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
K/N	None	None	0.782	N	0.57	0.161	0.166414681773	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
K/A	0.4778	ambiguous	0.3725	ambiguous	-0.142	Destabilizing	0.404	N	0.578	neutral	None	None	None	None	I
K/C	0.7614	likely_pathogenic	0.7219	pathogenic	-0.355	Destabilizing	0.991	D	0.811	deleterious	None	None	None	None	I
K/D	0.8333	likely_pathogenic	0.7533	pathogenic	0.216	Stabilizing	0.826	D	0.583	neutral	None	None	None	None	I
K/E	0.3972	ambiguous	0.3118	benign	0.272	Stabilizing	0.338	N	0.603	neutral	N	0.474056499	None	None	I
K/F	0.8788	likely_pathogenic	0.8307	pathogenic	-0.104	Destabilizing	0.967	D	0.731	prob.delet.	None	None	None	None	I
K/G	0.6519	likely_pathogenic	0.5575	ambiguous	-0.413	Destabilizing	0.575	D	0.551	neutral	None	None	None	None	I
K/H	0.4263	ambiguous	0.3793	ambiguous	-0.612	Destabilizing	0.947	D	0.635	neutral	None	None	None	None	I
K/I	0.4918	ambiguous	0.404	ambiguous	0.513	Stabilizing	0.879	D	0.738	prob.delet.	N	0.464679693	None	None	I
K/L	0.4472	ambiguous	0.372	ambiguous	0.513	Stabilizing	0.575	D	0.551	neutral	None	None	None	None	I
K/M	0.3697	ambiguous	0.2899	benign	0.2	Stabilizing	0.973	D	0.633	neutral	None	None	None	None	I
K/N	0.6843	likely_pathogenic	0.5776	pathogenic	-0.015	Destabilizing	0.782	D	0.57	neutral	N	0.479230006	None	None	I
K/P	0.9402	likely_pathogenic	0.8971	pathogenic	0.325	Stabilizing	0.906	D	0.649	neutral	None	None	None	None	I
K/Q	0.1935	likely_benign	0.1704	benign	-0.105	Destabilizing	0.007	N	0.213	neutral	N	0.479674825	None	None	I
K/R	0.0874	likely_benign	0.0851	benign	-0.184	Destabilizing	0.003	N	0.135	neutral	N	0.474457203	None	None	I
K/S	0.5768	likely_pathogenic	0.4509	ambiguous	-0.583	Destabilizing	0.404	N	0.558	neutral	None	None	None	None	I
K/T	0.206	likely_benign	0.1391	benign	-0.348	Destabilizing	0.782	D	0.593	neutral	N	0.373322991	None	None	I
K/V	0.4464	ambiguous	0.3661	ambiguous	0.325	Stabilizing	0.826	D	0.611	neutral	None	None	None	None	I
K/W	0.8405	likely_pathogenic	0.8056	pathogenic	-0.072	Destabilizing	0.991	D	0.814	deleterious	None	None	None	None	I
K/Y	0.7888	likely_pathogenic	0.7319	pathogenic	0.25	Stabilizing	0.906	D	0.723	prob.delet.	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.