TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15039	45340;45341;45342	chr2:178621709;178621708;178621707	chr2:179486436;179486435;179486434
N2AB	13398	40417;40418;40419	chr2:178621709;178621708;178621707	chr2:179486436;179486435;179486434
N2A	12471	37636;37637;37638	chr2:178621709;178621708;178621707	chr2:179486436;179486435;179486434
N2B	5974	18145;18146;18147	chr2:178621709;178621708;178621707	chr2:179486436;179486435;179486434
Novex-1	6099	18520;18521;18522	chr2:178621709;178621708;178621707	chr2:179486436;179486435;179486434
Novex-2	6166	18721;18722;18723	chr2:178621709;178621708;178621707	chr2:179486436;179486435;179486434
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-102
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6532
• 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	0.046	N	0.204	0.304	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/K	rs758487494	0.356	0.939	D	0.434	0.547	0.329282125956	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
N/K	rs758487494	0.356	0.939	D	0.434	0.547	0.329282125956	gnomAD-4.0.0	1.59571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43554E-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
N/A	0.2725	likely_benign	0.2976	benign	-0.179	Destabilizing	0.953	D	0.469	neutral	None	None	None	None	N
N/C	0.5676	likely_pathogenic	0.5691	pathogenic	0.296	Stabilizing	0.999	D	0.666	neutral	None	None	None	None	N
N/D	0.0866	likely_benign	0.1015	benign	0.176	Stabilizing	0.046	N	0.204	neutral	N	0.474258825	None	None	N
N/E	0.4582	ambiguous	0.5174	ambiguous	0.141	Stabilizing	0.91	D	0.411	neutral	None	None	None	None	N
N/F	0.7874	likely_pathogenic	0.7993	pathogenic	-0.583	Destabilizing	0.993	D	0.647	neutral	None	None	None	None	N
N/G	0.2925	likely_benign	0.3085	benign	-0.344	Destabilizing	0.953	D	0.425	neutral	None	None	None	None	N
N/H	0.1958	likely_benign	0.2116	benign	-0.365	Destabilizing	0.1	N	0.285	neutral	D	0.547898631	None	None	N
N/I	0.4538	ambiguous	0.476	ambiguous	0.162	Stabilizing	0.991	D	0.645	neutral	D	0.639296068	None	None	N
N/K	0.4866	ambiguous	0.576	pathogenic	0.146	Stabilizing	0.939	D	0.434	neutral	D	0.640643099	None	None	N
N/L	0.447	ambiguous	0.4697	ambiguous	0.162	Stabilizing	0.993	D	0.606	neutral	None	None	None	None	N
N/M	0.5645	likely_pathogenic	0.5845	pathogenic	0.33	Stabilizing	0.999	D	0.595	neutral	None	None	None	None	N
N/P	0.4101	ambiguous	0.44	ambiguous	0.075	Stabilizing	0.993	D	0.607	neutral	None	None	None	None	N
N/Q	0.4799	ambiguous	0.5423	ambiguous	-0.296	Destabilizing	0.993	D	0.463	neutral	None	None	None	None	N
N/R	0.5277	ambiguous	0.5978	pathogenic	0.174	Stabilizing	0.993	D	0.455	neutral	None	None	None	None	N
N/S	0.0914	likely_benign	0.0911	benign	-0.08	Destabilizing	0.939	D	0.453	neutral	N	0.484505094	None	None	N
N/T	0.2053	likely_benign	0.2284	benign	0.026	Stabilizing	0.969	D	0.432	neutral	D	0.548280043	None	None	N
N/V	0.4041	ambiguous	0.4209	ambiguous	0.075	Stabilizing	0.993	D	0.629	neutral	None	None	None	None	N
N/W	0.9079	likely_pathogenic	0.9179	pathogenic	-0.612	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
N/Y	0.3403	ambiguous	0.3677	ambiguous	-0.318	Destabilizing	0.982	D	0.608	neutral	D	0.639296068	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.