TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19167	57724;57725;57726	chr2:178597583;178597582;178597581	chr2:179462310;179462309;179462308
N2AB	17526	52801;52802;52803	chr2:178597583;178597582;178597581	chr2:179462310;179462309;179462308
N2A	16599	50020;50021;50022	chr2:178597583;178597582;178597581	chr2:179462310;179462309;179462308
N2B	10102	30529;30530;30531	chr2:178597583;178597582;178597581	chr2:179462310;179462309;179462308
Novex-1	10227	30904;30905;30906	chr2:178597583;178597582;178597581	chr2:179462310;179462309;179462308
Novex-2	10294	31105;31106;31107	chr2:178597583;178597582;178597581	chr2:179462310;179462309;179462308
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-117
• Domain position: 73
• Structural Position: 161
• Q(SASA): 0.1981
• 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
N/T	None	None	0.999	D	0.705	0.728	0.425970041486	gnomAD-4.0.0	4.78077E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.58222E-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
N/A	0.99	likely_pathogenic	0.9933	pathogenic	-0.527	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
N/C	0.934	likely_pathogenic	0.9548	pathogenic	0.062	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
N/D	0.9818	likely_pathogenic	0.9828	pathogenic	-1.291	Destabilizing	0.999	D	0.611	neutral	D	0.522304643	None	None	I
N/E	0.9967	likely_pathogenic	0.9974	pathogenic	-1.238	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	I
N/F	0.9991	likely_pathogenic	0.9992	pathogenic	-0.615	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
N/G	0.9655	likely_pathogenic	0.9755	pathogenic	-0.805	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	I
N/H	0.9742	likely_pathogenic	0.9787	pathogenic	-0.835	Destabilizing	1.0	D	0.747	deleterious	D	0.534928396	None	None	I
N/I	0.9916	likely_pathogenic	0.9928	pathogenic	0.153	Stabilizing	1.0	D	0.705	prob.neutral	D	0.535181885	None	None	I
N/K	0.9977	likely_pathogenic	0.9982	pathogenic	-0.226	Destabilizing	1.0	D	0.734	prob.delet.	D	0.534421416	None	None	I
N/L	0.9854	likely_pathogenic	0.9876	pathogenic	0.153	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
N/M	0.9863	likely_pathogenic	0.9892	pathogenic	0.74	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
N/P	0.9982	likely_pathogenic	0.9983	pathogenic	-0.045	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
N/Q	0.9965	likely_pathogenic	0.9973	pathogenic	-1.03	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
N/R	0.9968	likely_pathogenic	0.9975	pathogenic	-0.149	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
N/S	0.7619	likely_pathogenic	0.8218	pathogenic	-0.708	Destabilizing	0.999	D	0.579	neutral	N	0.506148944	None	None	I
N/T	0.9067	likely_pathogenic	0.9256	pathogenic	-0.504	Destabilizing	0.999	D	0.705	prob.neutral	D	0.522558132	None	None	I
N/V	0.9871	likely_pathogenic	0.9898	pathogenic	-0.045	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
N/W	0.9996	likely_pathogenic	0.9996	pathogenic	-0.504	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
N/Y	0.9897	likely_pathogenic	0.9912	pathogenic	-0.204	Destabilizing	1.0	D	0.727	prob.delet.	D	0.534928396	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.