TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21787	65584;65585;65586	chr2:178583823;178583822;178583821	chr2:179448550;179448549;179448548
N2AB	20146	60661;60662;60663	chr2:178583823;178583822;178583821	chr2:179448550;179448549;179448548
N2A	19219	57880;57881;57882	chr2:178583823;178583822;178583821	chr2:179448550;179448549;179448548
N2B	12722	38389;38390;38391	chr2:178583823;178583822;178583821	chr2:179448550;179448549;179448548
Novex-1	12847	38764;38765;38766	chr2:178583823;178583822;178583821	chr2:179448550;179448549;179448548
Novex-2	12914	38965;38966;38967	chr2:178583823;178583822;178583821	chr2:179448550;179448549;179448548
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-46
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2068
• 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/N	rs1290046297	None	0.999	N	0.701	0.292	0.272639205421	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/N	rs1290046297	None	0.999	N	0.701	0.292	0.272639205421	gnomAD-4.0.0	6.57661E-06	None	None	None	None	I	None	2.41383E-05	0	None	0	0	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	0.2346	likely_benign	0.2112	benign	-0.502	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	I
S/C	0.2143	likely_benign	0.1892	benign	-0.245	Destabilizing	1.0	D	0.741	deleterious	N	0.487021185	None	None	I
S/D	0.935	likely_pathogenic	0.9155	pathogenic	0.02	Stabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
S/E	0.9389	likely_pathogenic	0.9239	pathogenic	-0.058	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
S/F	0.665	likely_pathogenic	0.605	pathogenic	-1.023	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
S/G	0.3099	likely_benign	0.2842	benign	-0.647	Destabilizing	0.999	D	0.581	neutral	N	0.49107877	None	None	I
S/H	0.7711	likely_pathogenic	0.722	pathogenic	-1.234	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
S/I	0.7285	likely_pathogenic	0.6483	pathogenic	-0.246	Destabilizing	1.0	D	0.809	deleterious	N	0.494970449	None	None	I
S/K	0.9787	likely_pathogenic	0.9706	pathogenic	-0.529	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
S/L	0.3979	ambiguous	0.3444	ambiguous	-0.246	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
S/M	0.5392	ambiguous	0.4718	ambiguous	0.171	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
S/N	0.5904	likely_pathogenic	0.5253	ambiguous	-0.267	Destabilizing	0.999	D	0.701	prob.neutral	N	0.483614144	None	None	I
S/P	0.9744	likely_pathogenic	0.9697	pathogenic	-0.301	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
S/Q	0.8493	likely_pathogenic	0.8256	pathogenic	-0.546	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
S/R	0.962	likely_pathogenic	0.9493	pathogenic	-0.344	Destabilizing	1.0	D	0.777	deleterious	N	0.483725821	None	None	I
S/T	0.3748	ambiguous	0.3182	benign	-0.372	Destabilizing	0.999	D	0.587	neutral	N	0.480562724	None	None	I
S/V	0.6711	likely_pathogenic	0.5872	pathogenic	-0.301	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
S/W	0.712	likely_pathogenic	0.6654	pathogenic	-0.995	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
S/Y	0.5821	likely_pathogenic	0.5263	ambiguous	-0.728	Destabilizing	1.0	D	0.807	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.