TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5002	15229;15230;15231	chr2:178734920;178734919;178734918	chr2:179599647;179599646;179599645
N2AB	4685	14278;14279;14280	chr2:178734920;178734919;178734918	chr2:179599647;179599646;179599645
N2A	3758	11497;11498;11499	chr2:178734920;178734919;178734918	chr2:179599647;179599646;179599645
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-33
• Domain position: 22
• Structural Position: 31
• Q(SASA): 0.2938
• Predicted PPI site: N

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
H/N	None	None	0.425	N	0.334	0.172	0.260249123532	gnomAD-4.0.0	1.59585E-06	None	None	None	None	N	None	0	0	None	0	2.78691E-05	None	0	0	0	0	0
H/P	None	None	0.784	N	0.453	0.344	0.536988229258	gnomAD-4.0.0	1.59534E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43571E-05	0
H/Y	None	None	0.917	N	0.381	0.173	0.394230963961	gnomAD-4.0.0	1.59585E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03214E-05

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
H/A	0.2501	likely_benign	0.3301	benign	-0.469	Destabilizing	0.176	N	0.361	neutral	None	None	None	None	N
H/C	0.1867	likely_benign	0.2241	benign	0.408	Stabilizing	0.981	D	0.504	neutral	None	None	None	None	N
H/D	0.282	likely_benign	0.3575	ambiguous	-0.331	Destabilizing	0.001	N	0.194	neutral	N	0.426463142	None	None	N
H/E	0.2708	likely_benign	0.3482	ambiguous	-0.243	Destabilizing	0.085	N	0.271	neutral	None	None	None	None	N
H/F	0.2945	likely_benign	0.349	ambiguous	0.643	Stabilizing	0.981	D	0.535	neutral	None	None	None	None	N
H/G	0.3017	likely_benign	0.3905	ambiguous	-0.839	Destabilizing	0.3	N	0.393	neutral	None	None	None	None	N
H/I	0.2635	likely_benign	0.3267	benign	0.542	Stabilizing	0.828	D	0.539	neutral	None	None	None	None	N
H/K	0.2263	likely_benign	0.2561	benign	-0.333	Destabilizing	0.176	N	0.362	neutral	None	None	None	None	N
H/L	0.1044	likely_benign	0.131	benign	0.542	Stabilizing	0.425	N	0.431	neutral	N	0.480530439	None	None	N
H/M	0.4781	ambiguous	0.5512	ambiguous	0.407	Stabilizing	0.944	D	0.503	neutral	None	None	None	None	N
H/N	0.0996	likely_benign	0.1298	benign	-0.301	Destabilizing	0.425	N	0.334	neutral	N	0.460008538	None	None	N
H/P	0.2565	likely_benign	0.3256	benign	0.227	Stabilizing	0.784	D	0.453	neutral	N	0.453921508	None	None	N
H/Q	0.1363	likely_benign	0.1665	benign	-0.057	Destabilizing	0.003	N	0.119	neutral	N	0.423278262	None	None	N
H/R	0.0822	likely_benign	0.0895	benign	-1.001	Destabilizing	0.27	N	0.303	neutral	N	0.435680139	None	None	N
H/S	0.1922	likely_benign	0.2475	benign	-0.265	Destabilizing	0.037	N	0.199	neutral	None	None	None	None	N
H/T	0.2398	likely_benign	0.3125	benign	-0.075	Destabilizing	0.329	N	0.426	neutral	None	None	None	None	N
H/V	0.2115	likely_benign	0.2649	benign	0.227	Stabilizing	0.665	D	0.455	neutral	None	None	None	None	N
H/W	0.4076	ambiguous	0.4364	ambiguous	0.83	Stabilizing	0.995	D	0.501	neutral	None	None	None	None	N
H/Y	0.1025	likely_benign	0.1182	benign	0.976	Stabilizing	0.917	D	0.381	neutral	N	0.476249143	None	None	N

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.