TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22343	67252;67253;67254	chr2:178580352;178580351;178580350	chr2:179445079;179445078;179445077
N2AB	20702	62329;62330;62331	chr2:178580352;178580351;178580350	chr2:179445079;179445078;179445077
N2A	19775	59548;59549;59550	chr2:178580352;178580351;178580350	chr2:179445079;179445078;179445077
N2B	13278	40057;40058;40059	chr2:178580352;178580351;178580350	chr2:179445079;179445078;179445077
Novex-1	13403	40432;40433;40434	chr2:178580352;178580351;178580350	chr2:179445079;179445078;179445077
Novex-2	13470	40633;40634;40635	chr2:178580352;178580351;178580350	chr2:179445079;179445078;179445077
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-126
• Domain position: 79
• Structural Position: 166
• Q(SASA): 0.5203
• 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	1.0	N	0.723	0.384	0.317378411342	gnomAD-4.0.0	1.20037E-06	None	None	None	None	I	None	0	0	None	0	2.75634E-04	None	0	0	0	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	0.6643	likely_pathogenic	0.6837	pathogenic	-0.335	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
K/C	0.8635	likely_pathogenic	0.8767	pathogenic	-0.51	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
K/D	0.9282	likely_pathogenic	0.9253	pathogenic	0.041	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
K/E	0.5556	ambiguous	0.5421	ambiguous	0.13	Stabilizing	0.999	D	0.655	neutral	N	0.487730245	None	None	I
K/F	0.9656	likely_pathogenic	0.9675	pathogenic	-0.19	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
K/G	0.8395	likely_pathogenic	0.8469	pathogenic	-0.634	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
K/H	0.626	likely_pathogenic	0.6162	pathogenic	-0.782	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	I
K/I	0.7074	likely_pathogenic	0.7234	pathogenic	0.409	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
K/L	0.7507	likely_pathogenic	0.7634	pathogenic	0.409	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
K/M	0.5258	ambiguous	0.5288	ambiguous	-0.003	Destabilizing	1.0	D	0.629	neutral	N	0.52023268	None	None	I
K/N	0.8124	likely_pathogenic	0.8103	pathogenic	-0.228	Destabilizing	1.0	D	0.723	prob.delet.	N	0.492467186	None	None	I
K/P	0.9921	likely_pathogenic	0.9931	pathogenic	0.19	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
K/Q	0.2877	likely_benign	0.2821	benign	-0.252	Destabilizing	1.0	D	0.72	prob.delet.	N	0.483717774	None	None	I
K/R	0.1223	likely_benign	0.1193	benign	-0.268	Destabilizing	0.999	D	0.607	neutral	N	0.517743375	None	None	I
K/S	0.7792	likely_pathogenic	0.7927	pathogenic	-0.776	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
K/T	0.4411	ambiguous	0.4552	ambiguous	-0.497	Destabilizing	1.0	D	0.723	prob.delet.	D	0.526632217	None	None	I
K/V	0.5999	likely_pathogenic	0.6174	pathogenic	0.19	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
K/W	0.9542	likely_pathogenic	0.9557	pathogenic	-0.159	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
K/Y	0.9083	likely_pathogenic	0.912	pathogenic	0.142	Stabilizing	1.0	D	0.681	prob.neutral	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.