TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19069	57430;57431;57432	chr2:178597965;178597964;178597963	chr2:179462692;179462691;179462690
N2AB	17428	52507;52508;52509	chr2:178597965;178597964;178597963	chr2:179462692;179462691;179462690
N2A	16501	49726;49727;49728	chr2:178597965;178597964;178597963	chr2:179462692;179462691;179462690
N2B	10004	30235;30236;30237	chr2:178597965;178597964;178597963	chr2:179462692;179462691;179462690
Novex-1	10129	30610;30611;30612	chr2:178597965;178597964;178597963	chr2:179462692;179462691;179462690
Novex-2	10196	30811;30812;30813	chr2:178597965;178597964;178597963	chr2:179462692;179462691;179462690
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-26
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.3671
• 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
A/V	rs1477752765	None	1.0	N	0.717	0.42	0.494098832713	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/V	rs1477752765	None	1.0	N	0.717	0.42	0.494098832713	gnomAD-4.0.0	2.0301E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.40995E-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
A/C	0.5989	likely_pathogenic	0.5428	ambiguous	-0.873	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
A/D	0.9269	likely_pathogenic	0.8806	pathogenic	-0.647	Destabilizing	1.0	D	0.859	deleterious	N	0.489739756	None	None	I
A/E	0.8067	likely_pathogenic	0.7274	pathogenic	-0.805	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
A/F	0.6695	likely_pathogenic	0.6101	pathogenic	-1.011	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	I
A/G	0.3384	likely_benign	0.2813	benign	-0.477	Destabilizing	1.0	D	0.615	neutral	N	0.465595113	None	None	I
A/H	0.8739	likely_pathogenic	0.8287	pathogenic	-0.402	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
A/I	0.4724	ambiguous	0.4264	ambiguous	-0.507	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
A/K	0.928	likely_pathogenic	0.8777	pathogenic	-0.739	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
A/L	0.5148	ambiguous	0.4357	ambiguous	-0.507	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
A/M	0.5431	ambiguous	0.4781	ambiguous	-0.485	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
A/N	0.8005	likely_pathogenic	0.7303	pathogenic	-0.458	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
A/P	0.9449	likely_pathogenic	0.9245	pathogenic	-0.449	Destabilizing	1.0	D	0.813	deleterious	N	0.520974743	None	None	I
A/Q	0.7953	likely_pathogenic	0.7189	pathogenic	-0.772	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
A/R	0.8582	likely_pathogenic	0.7803	pathogenic	-0.194	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
A/S	0.2055	likely_benign	0.185	benign	-0.656	Destabilizing	1.0	D	0.619	neutral	N	0.472395969	None	None	I
A/T	0.3269	likely_benign	0.2643	benign	-0.738	Destabilizing	1.0	D	0.772	deleterious	N	0.483916859	None	None	I
A/V	0.2261	likely_benign	0.1989	benign	-0.449	Destabilizing	1.0	D	0.717	prob.delet.	N	0.446600061	None	None	I
A/W	0.9569	likely_pathogenic	0.9352	pathogenic	-1.108	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
A/Y	0.8585	likely_pathogenic	0.8131	pathogenic	-0.787	Destabilizing	1.0	D	0.877	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.