TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29999	90220;90221;90222	chr2:178552905;178552904;178552903	chr2:179417632;179417631;179417630
N2AB	28358	85297;85298;85299	chr2:178552905;178552904;178552903	chr2:179417632;179417631;179417630
N2A	27431	82516;82517;82518	chr2:178552905;178552904;178552903	chr2:179417632;179417631;179417630
N2B	20934	63025;63026;63027	chr2:178552905;178552904;178552903	chr2:179417632;179417631;179417630
Novex-1	21059	63400;63401;63402	chr2:178552905;178552904;178552903	chr2:179417632;179417631;179417630
Novex-2	21126	63601;63602;63603	chr2:178552905;178552904;178552903	chr2:179417632;179417631;179417630
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-106
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.379
• 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
E/V	rs1249458719	None	0.961	N	0.411	0.295	0.592282861509	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85802E-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
E/A	0.2932	likely_benign	0.2739	benign	-0.554	Destabilizing	0.98	D	0.368	neutral	N	0.465973507	None	None	N
E/C	0.9355	likely_pathogenic	0.9266	pathogenic	0.092	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	N
E/D	0.2294	likely_benign	0.2183	benign	-0.491	Destabilizing	0.997	D	0.506	neutral	N	0.507870464	None	None	N
E/F	0.9109	likely_pathogenic	0.9013	pathogenic	-0.578	Destabilizing	0.996	D	0.588	neutral	None	None	None	None	N
E/G	0.2553	likely_benign	0.2301	benign	-0.773	Destabilizing	0.997	D	0.445	neutral	N	0.504996855	None	None	N
E/H	0.7459	likely_pathogenic	0.7114	pathogenic	-0.712	Destabilizing	1.0	D	0.427	neutral	None	None	None	None	N
E/I	0.5971	likely_pathogenic	0.5808	pathogenic	-0.001	Destabilizing	0.671	D	0.341	neutral	None	None	None	None	N
E/K	0.2985	likely_benign	0.2804	benign	0.238	Stabilizing	0.99	D	0.501	neutral	N	0.48990434	None	None	N
E/L	0.6413	likely_pathogenic	0.6255	pathogenic	-0.001	Destabilizing	0.931	D	0.465	neutral	None	None	None	None	N
E/M	0.7068	likely_pathogenic	0.6847	pathogenic	0.368	Stabilizing	0.931	D	0.324	neutral	None	None	None	None	N
E/N	0.4914	ambiguous	0.4576	ambiguous	-0.019	Destabilizing	0.999	D	0.441	neutral	None	None	None	None	N
E/P	0.5564	ambiguous	0.5377	ambiguous	-0.165	Destabilizing	0.999	D	0.419	neutral	None	None	None	None	N
E/Q	0.2378	likely_benign	0.2201	benign	None	Stabilizing	0.997	D	0.487	neutral	N	0.481928623	None	None	N
E/R	0.4903	ambiguous	0.4673	ambiguous	0.252	Stabilizing	0.998	D	0.443	neutral	None	None	None	None	N
E/S	0.3556	ambiguous	0.3223	benign	-0.203	Destabilizing	0.993	D	0.459	neutral	None	None	None	None	N
E/T	0.4488	ambiguous	0.4285	ambiguous	-0.023	Destabilizing	0.993	D	0.362	neutral	None	None	None	None	N
E/V	0.3949	ambiguous	0.3803	ambiguous	-0.165	Destabilizing	0.961	D	0.411	neutral	N	0.489766209	None	None	N
E/W	0.9638	likely_pathogenic	0.958	pathogenic	-0.449	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
E/Y	0.8508	likely_pathogenic	0.8347	pathogenic	-0.335	Destabilizing	0.999	D	0.543	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.