TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5365	16318;16319;16320	chr2:178733083;178733082;178733081	chr2:179597810;179597809;179597808
N2AB	5048	15367;15368;15369	chr2:178733083;178733082;178733081	chr2:179597810;179597809;179597808
N2A	4121	12586;12587;12588	chr2:178733083;178733082;178733081	chr2:179597810;179597809;179597808
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-37
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6885
• 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
N/D	None	None	0.002	N	0.104	0.121	0.112648838833	gnomAD-4.0.0	1.37739E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80837E-06	0	0
N/I	rs2080837550	None	0.487	N	0.384	0.189	0.450152462452	gnomAD-4.0.0	1.60988E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89491E-06	0	0
N/K	rs72648935	0.497	0.018	N	0.093	0.057	0.0297737177859	gnomAD-2.1.1	4.12E-06	None	None	None	None	N	None	0	2.97E-05	None	0	0	None	0	None	0	0	0
N/K	rs72648935	0.497	0.018	N	0.093	0.057	0.0297737177859	gnomAD-4.0.0	6.87793E-07	None	None	None	None	N	None	0	2.26613E-05	None	0	0	None	0	0	0	0	0
N/Y	rs878854288	-0.396	0.794	N	0.315	0.328	0.44750879378	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	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
N/A	0.2135	likely_benign	0.2248	benign	-0.231	Destabilizing	0.129	N	0.289	neutral	None	None	None	None	N
N/C	0.4174	ambiguous	0.4282	ambiguous	0.361	Stabilizing	0.983	D	0.3	neutral	None	None	None	None	N
N/D	0.1112	likely_benign	0.1089	benign	0.098	Stabilizing	0.002	N	0.104	neutral	N	0.411665476	None	None	N
N/E	0.3429	ambiguous	0.3489	ambiguous	0.061	Stabilizing	0.129	N	0.297	neutral	None	None	None	None	N
N/F	0.6059	likely_pathogenic	0.6271	pathogenic	-0.624	Destabilizing	0.836	D	0.327	neutral	None	None	None	None	N
N/G	0.2681	likely_benign	0.2795	benign	-0.399	Destabilizing	0.228	N	0.281	neutral	None	None	None	None	N
N/H	0.1333	likely_benign	0.1347	benign	-0.456	Destabilizing	0.794	D	0.363	neutral	N	0.457390862	None	None	N
N/I	0.2728	likely_benign	0.2877	benign	0.122	Stabilizing	0.487	N	0.384	neutral	N	0.481002072	None	None	N
N/K	0.2721	likely_benign	0.2675	benign	0.114	Stabilizing	0.018	N	0.093	neutral	N	0.515160777	None	None	N
N/L	0.2825	likely_benign	0.2955	benign	0.122	Stabilizing	0.264	N	0.37	neutral	None	None	None	None	N
N/M	0.3463	ambiguous	0.3588	ambiguous	0.39	Stabilizing	0.836	D	0.308	neutral	None	None	None	None	N
N/P	0.3461	ambiguous	0.3833	ambiguous	0.031	Stabilizing	0.593	D	0.397	neutral	None	None	None	None	N
N/Q	0.3235	likely_benign	0.3291	benign	-0.307	Destabilizing	0.027	N	0.215	neutral	None	None	None	None	N
N/R	0.3098	likely_benign	0.3135	benign	0.148	Stabilizing	0.001	N	0.076	neutral	None	None	None	None	N
N/S	0.0962	likely_benign	0.0969	benign	-0.073	Destabilizing	0.101	N	0.334	neutral	N	0.464230524	None	None	N
N/T	0.147	likely_benign	0.1511	benign	0.029	Stabilizing	0.002	N	0.129	neutral	N	0.511312395	None	None	N
N/V	0.2693	likely_benign	0.2837	benign	0.031	Stabilizing	0.264	N	0.399	neutral	None	None	None	None	N
N/W	0.788	likely_pathogenic	0.8027	pathogenic	-0.642	Destabilizing	0.983	D	0.356	neutral	None	None	None	None	N
N/Y	0.2044	likely_benign	0.2041	benign	-0.359	Destabilizing	0.794	D	0.315	neutral	N	0.481255562	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.