TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27597	83014;83015;83016	chr2:178563343;178563342;178563341	chr2:179428070;179428069;179428068
N2AB	25956	78091;78092;78093	chr2:178563343;178563342;178563341	chr2:179428070;179428069;179428068
N2A	25029	75310;75311;75312	chr2:178563343;178563342;178563341	chr2:179428070;179428069;179428068
N2B	18532	55819;55820;55821	chr2:178563343;178563342;178563341	chr2:179428070;179428069;179428068
Novex-1	18657	56194;56195;56196	chr2:178563343;178563342;178563341	chr2:179428070;179428069;179428068
Novex-2	18724	56395;56396;56397	chr2:178563343;178563342;178563341	chr2:179428070;179428069;179428068
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-89
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2842
• 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
D/H	None	None	1.0	N	0.651	0.581	0.519024713989	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
D/A	0.8861	likely_pathogenic	0.8576	pathogenic	-0.666	Destabilizing	1.0	D	0.714	prob.delet.	N	0.496349574	None	None	I
D/C	0.9705	likely_pathogenic	0.962	pathogenic	-0.372	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
D/E	0.8345	likely_pathogenic	0.8088	pathogenic	-0.75	Destabilizing	1.0	D	0.443	neutral	N	0.493196023	None	None	I
D/F	0.9837	likely_pathogenic	0.9823	pathogenic	-0.415	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I
D/G	0.8206	likely_pathogenic	0.8125	pathogenic	-1.043	Destabilizing	1.0	D	0.699	prob.neutral	N	0.493262156	None	None	I
D/H	0.9136	likely_pathogenic	0.8892	pathogenic	-0.892	Destabilizing	1.0	D	0.651	neutral	N	0.511099695	None	None	I
D/I	0.973	likely_pathogenic	0.9622	pathogenic	0.344	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	I
D/K	0.9734	likely_pathogenic	0.9653	pathogenic	-0.766	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
D/L	0.9593	likely_pathogenic	0.9536	pathogenic	0.344	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
D/M	0.9878	likely_pathogenic	0.9857	pathogenic	0.889	Stabilizing	1.0	D	0.636	neutral	None	None	None	None	I
D/N	0.2957	likely_benign	0.28	benign	-1.094	Destabilizing	1.0	D	0.698	prob.neutral	N	0.481790492	None	None	I
D/P	0.9818	likely_pathogenic	0.9807	pathogenic	0.032	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/Q	0.9521	likely_pathogenic	0.9385	pathogenic	-0.903	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/R	0.9609	likely_pathogenic	0.9492	pathogenic	-0.72	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
D/S	0.5682	likely_pathogenic	0.5294	ambiguous	-1.453	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
D/T	0.8464	likely_pathogenic	0.8104	pathogenic	-1.136	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
D/V	0.9269	likely_pathogenic	0.9003	pathogenic	0.032	Stabilizing	1.0	D	0.694	prob.neutral	N	0.517340665	None	None	I
D/W	0.9953	likely_pathogenic	0.9946	pathogenic	-0.351	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	I
D/Y	0.8798	likely_pathogenic	0.8596	pathogenic	-0.214	Destabilizing	1.0	D	0.626	neutral	D	0.548068673	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.