TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18850	56773;56774;56775	chr2:178599245;178599244;178599243	chr2:179463972;179463971;179463970
N2AB	17209	51850;51851;51852	chr2:178599245;178599244;178599243	chr2:179463972;179463971;179463970
N2A	16282	49069;49070;49071	chr2:178599245;178599244;178599243	chr2:179463972;179463971;179463970
N2B	9785	29578;29579;29580	chr2:178599245;178599244;178599243	chr2:179463972;179463971;179463970
Novex-1	9910	29953;29954;29955	chr2:178599245;178599244;178599243	chr2:179463972;179463971;179463970
Novex-2	9977	30154;30155;30156	chr2:178599245;178599244;178599243	chr2:179463972;179463971;179463970
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-24
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.5226
• 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
L/P	None	None	0.989	N	0.415	0.324	0.663006186912	gnomAD-4.0.0	1.75332E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.74752E-05	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
L/A	0.3847	ambiguous	0.3607	ambiguous	-1.466	Destabilizing	0.525	D	0.341	neutral	None	None	None	None	N
L/C	0.7249	likely_pathogenic	0.6766	pathogenic	-0.776	Destabilizing	0.998	D	0.381	neutral	None	None	None	None	N
L/D	0.9062	likely_pathogenic	0.889	pathogenic	-0.837	Destabilizing	0.974	D	0.408	neutral	None	None	None	None	N
L/E	0.63	likely_pathogenic	0.5758	pathogenic	-0.839	Destabilizing	0.974	D	0.391	neutral	None	None	None	None	N
L/F	0.3058	likely_benign	0.2993	benign	-1.028	Destabilizing	0.949	D	0.374	neutral	None	None	None	None	N
L/G	0.7509	likely_pathogenic	0.7102	pathogenic	-1.771	Destabilizing	0.974	D	0.379	neutral	None	None	None	None	N
L/H	0.4154	ambiguous	0.381	ambiguous	-0.856	Destabilizing	0.998	D	0.391	neutral	None	None	None	None	N
L/I	0.1387	likely_benign	0.1346	benign	-0.711	Destabilizing	0.051	N	0.159	neutral	N	0.405369514	None	None	N
L/K	0.4258	ambiguous	0.3917	ambiguous	-0.9	Destabilizing	0.949	D	0.38	neutral	None	None	None	None	N
L/M	0.1262	likely_benign	0.137	benign	-0.567	Destabilizing	0.325	N	0.273	neutral	None	None	None	None	N
L/N	0.6106	likely_pathogenic	0.5895	pathogenic	-0.7	Destabilizing	0.974	D	0.412	neutral	None	None	None	None	N
L/P	0.7537	likely_pathogenic	0.7665	pathogenic	-0.931	Destabilizing	0.989	D	0.415	neutral	N	0.486889245	None	None	N
L/Q	0.2328	likely_benign	0.2171	benign	-0.873	Destabilizing	0.966	D	0.409	neutral	N	0.426339432	None	None	N
L/R	0.3516	ambiguous	0.318	benign	-0.29	Destabilizing	0.966	D	0.409	neutral	N	0.408868392	None	None	N
L/S	0.4891	ambiguous	0.4704	ambiguous	-1.288	Destabilizing	0.728	D	0.418	neutral	None	None	None	None	N
L/T	0.2557	likely_benign	0.2561	benign	-1.17	Destabilizing	0.067	N	0.15	neutral	None	None	None	None	N
L/V	0.1424	likely_benign	0.1377	benign	-0.931	Destabilizing	0.012	N	0.087	neutral	N	0.417066588	None	None	N
L/W	0.4365	ambiguous	0.4079	ambiguous	-1.073	Destabilizing	0.998	D	0.452	neutral	None	None	None	None	N
L/Y	0.606	likely_pathogenic	0.5719	pathogenic	-0.854	Destabilizing	0.974	D	0.396	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.