TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16480	49663;49664;49665	chr2:178613845;178613844;178613843	chr2:179478572;179478571;179478570
N2AB	14839	44740;44741;44742	chr2:178613845;178613844;178613843	chr2:179478572;179478571;179478570
N2A	13912	41959;41960;41961	chr2:178613845;178613844;178613843	chr2:179478572;179478571;179478570
N2B	7415	22468;22469;22470	chr2:178613845;178613844;178613843	chr2:179478572;179478571;179478570
Novex-1	7540	22843;22844;22845	chr2:178613845;178613844;178613843	chr2:179478572;179478571;179478570
Novex-2	7607	23044;23045;23046	chr2:178613845;178613844;178613843	chr2:179478572;179478571;179478570
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-7
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2481
• 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
S/R	None	None	1.0	D	0.791	0.445	0.365703291355	gnomAD-4.0.0	1.59398E-06	None	None	None	None	I	None	0	0	None	0	2.77824E-05	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
S/A	0.3195	likely_benign	0.2919	benign	-0.52	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	I
S/C	0.2112	likely_benign	0.1785	benign	-0.318	Destabilizing	1.0	D	0.757	deleterious	N	0.521997856	None	None	I
S/D	0.963	likely_pathogenic	0.943	pathogenic	-0.101	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	I
S/E	0.9759	likely_pathogenic	0.9676	pathogenic	-0.165	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	I
S/F	0.7817	likely_pathogenic	0.7351	pathogenic	-0.948	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
S/G	0.5004	ambiguous	0.4307	ambiguous	-0.692	Destabilizing	0.999	D	0.584	neutral	N	0.502744456	None	None	I
S/H	0.7906	likely_pathogenic	0.7347	pathogenic	-1.253	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
S/I	0.7921	likely_pathogenic	0.7418	pathogenic	-0.189	Destabilizing	1.0	D	0.817	deleterious	D	0.618837151	None	None	I
S/K	0.9865	likely_pathogenic	0.9851	pathogenic	-0.61	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	I
S/L	0.4682	ambiguous	0.4272	ambiguous	-0.189	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
S/M	0.6171	likely_pathogenic	0.5506	ambiguous	0.174	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
S/N	0.4756	ambiguous	0.3885	ambiguous	-0.391	Destabilizing	0.999	D	0.722	prob.delet.	D	0.574929214	None	None	I
S/P	0.9962	likely_pathogenic	0.9956	pathogenic	-0.268	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
S/Q	0.9297	likely_pathogenic	0.9098	pathogenic	-0.65	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
S/R	0.9806	likely_pathogenic	0.979	pathogenic	-0.415	Destabilizing	1.0	D	0.791	deleterious	D	0.577852441	None	None	I
S/T	0.4188	ambiguous	0.321	benign	-0.462	Destabilizing	0.999	D	0.599	neutral	D	0.543408199	None	None	I
S/V	0.7614	likely_pathogenic	0.6965	pathogenic	-0.268	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
S/W	0.9017	likely_pathogenic	0.8752	pathogenic	-0.918	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
S/Y	0.6993	likely_pathogenic	0.6565	pathogenic	-0.657	Destabilizing	1.0	D	0.821	deleterious	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.