TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5472	16639;16640;16641	chr2:178732647;178732646;178732645	chr2:179597374;179597373;179597372
N2AB	5155	15688;15689;15690	chr2:178732647;178732646;178732645	chr2:179597374;179597373;179597372
N2A	4228	12907;12908;12909	chr2:178732647;178732646;178732645	chr2:179597374;179597373;179597372
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-38
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.193
• 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
T/I	rs911246876	None	0.062	N	0.522	0.171	0.348101942276	gnomAD-4.0.0	1.59357E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02792E-05
T/S	rs911246876	None	0.005	N	0.192	0.073	0.260249123532	gnomAD-4.0.0	1.59357E-06	None	None	None	None	N	None	0	0	None	0	2.78133E-05	None	0	0	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
T/A	0.0684	likely_benign	0.0699	benign	-1.201	Destabilizing	None	N	0.177	neutral	N	0.4540414	None	None	N
T/C	0.3429	ambiguous	0.3383	benign	-0.792	Destabilizing	0.555	D	0.534	neutral	None	None	None	None	N
T/D	0.2919	likely_benign	0.3388	benign	-0.324	Destabilizing	0.149	N	0.525	neutral	None	None	None	None	N
T/E	0.2431	likely_benign	0.2709	benign	-0.259	Destabilizing	0.149	N	0.485	neutral	None	None	None	None	N
T/F	0.1862	likely_benign	0.1953	benign	-1.15	Destabilizing	0.38	N	0.584	neutral	None	None	None	None	N
T/G	0.21	likely_benign	0.212	benign	-1.497	Destabilizing	0.035	N	0.521	neutral	None	None	None	None	N
T/H	0.1854	likely_benign	0.1899	benign	-1.622	Destabilizing	0.935	D	0.579	neutral	None	None	None	None	N
T/I	0.1148	likely_benign	0.1233	benign	-0.476	Destabilizing	0.062	N	0.522	neutral	N	0.411445416	None	None	N
T/K	0.1433	likely_benign	0.1527	benign	-0.562	Destabilizing	0.149	N	0.485	neutral	None	None	None	None	N
T/L	0.0979	likely_benign	0.1007	benign	-0.476	Destabilizing	0.012	N	0.458	neutral	None	None	None	None	N
T/M	0.0987	likely_benign	0.0986	benign	-0.262	Destabilizing	0.005	N	0.352	neutral	None	None	None	None	N
T/N	0.1091	likely_benign	0.1153	benign	-0.679	Destabilizing	0.117	N	0.498	neutral	N	0.464546395	None	None	N
T/P	0.2787	likely_benign	0.3158	benign	-0.687	Destabilizing	0.317	N	0.542	neutral	N	0.45050245	None	None	N
T/Q	0.1776	likely_benign	0.1823	benign	-0.797	Destabilizing	0.555	D	0.559	neutral	None	None	None	None	N
T/R	0.103	likely_benign	0.1086	benign	-0.436	Destabilizing	0.38	N	0.543	neutral	None	None	None	None	N
T/S	0.0846	likely_benign	0.0855	benign	-1.082	Destabilizing	0.005	N	0.192	neutral	N	0.433935487	None	None	N
T/V	0.0978	likely_benign	0.101	benign	-0.687	Destabilizing	0.035	N	0.473	neutral	None	None	None	None	N
T/W	0.5225	ambiguous	0.5419	ambiguous	-1.023	Destabilizing	0.935	D	0.603	neutral	None	None	None	None	N
T/Y	0.2111	likely_benign	0.2235	benign	-0.774	Destabilizing	0.555	D	0.596	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.