TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15907	47944;47945;47946	chr2:178617366;178617365;178617364	chr2:179482093;179482092;179482091
N2AB	14266	43021;43022;43023	chr2:178617366;178617365;178617364	chr2:179482093;179482092;179482091
N2A	13339	40240;40241;40242	chr2:178617366;178617365;178617364	chr2:179482093;179482092;179482091
N2B	6842	20749;20750;20751	chr2:178617366;178617365;178617364	chr2:179482093;179482092;179482091
Novex-1	6967	21124;21125;21126	chr2:178617366;178617365;178617364	chr2:179482093;179482092;179482091
Novex-2	7034	21325;21326;21327	chr2:178617366;178617365;178617364	chr2:179482093;179482092;179482091
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-3
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.3357
• 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
I/F	None	None	0.002	N	0.147	0.159	0.318540980066	gnomAD-4.0.0	4.88482E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.35601E-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
I/A	0.4361	ambiguous	0.5223	ambiguous	-1.32	Destabilizing	0.129	N	0.317	neutral	None	None	None	None	I
I/C	0.65	likely_pathogenic	0.6972	pathogenic	-0.627	Destabilizing	0.983	D	0.323	neutral	None	None	None	None	I
I/D	0.6097	likely_pathogenic	0.6539	pathogenic	-0.696	Destabilizing	0.716	D	0.373	neutral	None	None	None	None	I
I/E	0.339	likely_benign	0.3448	ambiguous	-0.741	Destabilizing	0.716	D	0.37	neutral	None	None	None	None	I
I/F	0.1639	likely_benign	0.1964	benign	-1.013	Destabilizing	0.002	N	0.147	neutral	N	0.475837099	None	None	I
I/G	0.6561	likely_pathogenic	0.7123	pathogenic	-1.583	Destabilizing	0.418	N	0.335	neutral	None	None	None	None	I
I/H	0.3276	likely_benign	0.3486	ambiguous	-0.761	Destabilizing	0.983	D	0.322	neutral	None	None	None	None	I
I/K	0.1957	likely_benign	0.1855	benign	-0.805	Destabilizing	0.716	D	0.36	neutral	None	None	None	None	I
I/L	0.1062	likely_benign	0.1209	benign	-0.702	Destabilizing	None	N	0.087	neutral	N	0.428703186	None	None	I
I/M	0.1019	likely_benign	0.1126	benign	-0.475	Destabilizing	0.655	D	0.375	neutral	N	0.476261585	None	None	I
I/N	0.2137	likely_benign	0.2252	benign	-0.509	Destabilizing	0.655	D	0.376	neutral	N	0.475564153	None	None	I
I/P	0.906	likely_pathogenic	0.9094	pathogenic	-0.875	Destabilizing	0.836	D	0.363	neutral	None	None	None	None	I
I/Q	0.2288	likely_benign	0.2388	benign	-0.744	Destabilizing	0.836	D	0.341	neutral	None	None	None	None	I
I/R	0.1874	likely_benign	0.1806	benign	-0.159	Destabilizing	0.716	D	0.364	neutral	None	None	None	None	I
I/S	0.3231	likely_benign	0.3576	ambiguous	-1.058	Destabilizing	0.213	N	0.311	neutral	N	0.465614306	None	None	I
I/T	0.2839	likely_benign	0.3547	ambiguous	-0.996	Destabilizing	0.002	N	0.161	neutral	N	0.457236442	None	None	I
I/V	0.0972	likely_benign	0.112	benign	-0.875	Destabilizing	0.001	N	0.121	neutral	N	0.435329085	None	None	I
I/W	0.6217	likely_pathogenic	0.6802	pathogenic	-1.037	Destabilizing	0.983	D	0.329	neutral	None	None	None	None	I
I/Y	0.3756	ambiguous	0.3831	ambiguous	-0.827	Destabilizing	0.557	D	0.369	neutral	None	None	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.