TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21827	65704;65705;65706	chr2:178583703;178583702;178583701	chr2:179448430;179448429;179448428
N2AB	20186	60781;60782;60783	chr2:178583703;178583702;178583701	chr2:179448430;179448429;179448428
N2A	19259	58000;58001;58002	chr2:178583703;178583702;178583701	chr2:179448430;179448429;179448428
N2B	12762	38509;38510;38511	chr2:178583703;178583702;178583701	chr2:179448430;179448429;179448428
Novex-1	12887	38884;38885;38886	chr2:178583703;178583702;178583701	chr2:179448430;179448429;179448428
Novex-2	12954	39085;39086;39087	chr2:178583703;178583702;178583701	chr2:179448430;179448429;179448428
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-46
• Domain position: 71
• Structural Position: 100
• Q(SASA): 0.7415
• 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
K/Q	None	None	0.033	N	0.418	0.078	0.112648838833	gnomAD-4.0.0	1.59444E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43637E-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
K/A	0.1526	likely_benign	0.1438	benign	0.043	Stabilizing	0.004	N	0.28	neutral	None	None	None	None	N
K/C	0.3918	ambiguous	0.3648	ambiguous	-0.304	Destabilizing	0.788	D	0.455	neutral	None	None	None	None	N
K/D	0.1123	likely_benign	0.1202	benign	-0.062	Destabilizing	0.004	N	0.331	neutral	None	None	None	None	N
K/E	0.1056	likely_benign	0.0955	benign	-0.039	Destabilizing	0.003	N	0.239	neutral	N	0.417797306	None	None	N
K/F	0.5222	ambiguous	0.4781	ambiguous	-0.086	Destabilizing	0.497	N	0.495	neutral	None	None	None	None	N
K/G	0.0944	likely_benign	0.096	benign	-0.171	Destabilizing	None	N	0.241	neutral	None	None	None	None	N
K/H	0.1271	likely_benign	0.1198	benign	-0.341	Destabilizing	0.138	N	0.439	neutral	None	None	None	None	N
K/I	0.3526	ambiguous	0.3326	benign	0.532	Stabilizing	0.065	N	0.514	neutral	N	0.503320135	None	None	N
K/L	0.2212	likely_benign	0.2079	benign	0.532	Stabilizing	0.018	N	0.46	neutral	None	None	None	None	N
K/M	0.1408	likely_benign	0.14	benign	0.135	Stabilizing	0.497	N	0.435	neutral	None	None	None	None	N
K/N	0.0557	likely_benign	0.0621	benign	0.087	Stabilizing	None	N	0.155	neutral	N	0.390341346	None	None	N
K/P	0.5452	ambiguous	0.5687	pathogenic	0.397	Stabilizing	0.085	N	0.51	neutral	None	None	None	None	N
K/Q	0.0988	likely_benign	0.0878	benign	-0.036	Destabilizing	0.033	N	0.418	neutral	N	0.437980578	None	None	N
K/R	0.0963	likely_benign	0.0855	benign	-0.069	Destabilizing	0.014	N	0.403	neutral	N	0.443367755	None	None	N
K/S	0.1096	likely_benign	0.11	benign	-0.348	Destabilizing	0.004	N	0.227	neutral	None	None	None	None	N
K/T	0.1006	likely_benign	0.0977	benign	-0.175	Destabilizing	0.007	N	0.411	neutral	N	0.446773419	None	None	N
K/V	0.3041	likely_benign	0.2791	benign	0.397	Stabilizing	0.085	N	0.462	neutral	None	None	None	None	N
K/W	0.6052	likely_pathogenic	0.5835	pathogenic	-0.131	Destabilizing	0.788	D	0.457	neutral	None	None	None	None	N
K/Y	0.2656	likely_benign	0.2616	benign	0.214	Stabilizing	0.497	N	0.491	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.