TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24265	73018;73019;73020	chr2:178573339;178573338;178573337	chr2:179438066;179438065;179438064
N2AB	22624	68095;68096;68097	chr2:178573339;178573338;178573337	chr2:179438066;179438065;179438064
N2A	21697	65314;65315;65316	chr2:178573339;178573338;178573337	chr2:179438066;179438065;179438064
N2B	15200	45823;45824;45825	chr2:178573339;178573338;178573337	chr2:179438066;179438065;179438064
Novex-1	15325	46198;46199;46200	chr2:178573339;178573338;178573337	chr2:179438066;179438065;179438064
Novex-2	15392	46399;46400;46401	chr2:178573339;178573338;178573337	chr2:179438066;179438065;179438064
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: Fn3-64
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.6955
• 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
A/S	None	None	0.001	N	0.207	0.08	0.0884992946249	gnomAD-4.0.0	1.787E-06	None	None	None	None	N	None	0	0	None	6.00673E-05	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
A/C	0.3539	ambiguous	0.3372	benign	-0.701	Destabilizing	0.944	D	0.225	neutral	None	None	None	None	N
A/D	0.2382	likely_benign	0.2078	benign	-0.544	Destabilizing	0.324	N	0.329	neutral	N	0.408193601	None	None	N
A/E	0.2282	likely_benign	0.2027	benign	-0.693	Destabilizing	0.241	N	0.27	neutral	None	None	None	None	N
A/F	0.2637	likely_benign	0.2261	benign	-0.86	Destabilizing	0.818	D	0.374	neutral	None	None	None	None	N
A/G	0.1253	likely_benign	0.1086	benign	-0.177	Destabilizing	0.001	N	0.173	neutral	N	0.394397585	None	None	N
A/H	0.3555	ambiguous	0.328	benign	-0.199	Destabilizing	0.944	D	0.372	neutral	None	None	None	None	N
A/I	0.1758	likely_benign	0.1608	benign	-0.311	Destabilizing	0.527	D	0.271	neutral	None	None	None	None	N
A/K	0.3882	ambiguous	0.3486	ambiguous	-0.536	Destabilizing	0.241	N	0.262	neutral	None	None	None	None	N
A/L	0.1313	likely_benign	0.1199	benign	-0.311	Destabilizing	0.241	N	0.242	neutral	None	None	None	None	N
A/M	0.1518	likely_benign	0.143	benign	-0.499	Destabilizing	0.944	D	0.263	neutral	None	None	None	None	N
A/N	0.1624	likely_benign	0.1501	benign	-0.176	Destabilizing	0.241	N	0.363	neutral	None	None	None	None	N
A/P	0.387	ambiguous	0.3378	benign	-0.234	Destabilizing	0.773	D	0.27	neutral	N	0.455219544	None	None	N
A/Q	0.2677	likely_benign	0.2493	benign	-0.441	Destabilizing	0.69	D	0.277	neutral	None	None	None	None	N
A/R	0.3697	ambiguous	0.3268	benign	-0.104	Destabilizing	0.69	D	0.284	neutral	None	None	None	None	N
A/S	0.0852	likely_benign	0.0836	benign	-0.339	Destabilizing	0.001	N	0.207	neutral	N	0.385338171	None	None	N
A/T	0.0726	likely_benign	0.0724	benign	-0.417	Destabilizing	0.001	N	0.121	neutral	N	0.394843089	None	None	N
A/V	0.1026	likely_benign	0.0969	benign	-0.234	Destabilizing	0.193	N	0.234	neutral	N	0.456046263	None	None	N
A/W	0.6237	likely_pathogenic	0.5574	ambiguous	-0.988	Destabilizing	0.981	D	0.479	neutral	None	None	None	None	N
A/Y	0.3509	ambiguous	0.309	benign	-0.653	Destabilizing	0.818	D	0.372	neutral	None	None	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.