TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26343	79252;79253;79254	chr2:178567105;178567104;178567103	chr2:179431832;179431831;179431830
N2AB	24702	74329;74330;74331	chr2:178567105;178567104;178567103	chr2:179431832;179431831;179431830
N2A	23775	71548;71549;71550	chr2:178567105;178567104;178567103	chr2:179431832;179431831;179431830
N2B	17278	52057;52058;52059	chr2:178567105;178567104;178567103	chr2:179431832;179431831;179431830
Novex-1	17403	52432;52433;52434	chr2:178567105;178567104;178567103	chr2:179431832;179431831;179431830
Novex-2	17470	52633;52634;52635	chr2:178567105;178567104;178567103	chr2:179431832;179431831;179431830
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-79
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.3306
• 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	rs765936549	0.131	0.934	N	0.42	0.444	0.419090007872	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
T/I	rs765936549	0.131	0.934	N	0.42	0.444	0.419090007872	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
T/I	rs765936549	0.131	0.934	N	0.42	0.444	0.419090007872	gnomAD-4.0.0	4.21473E-05	None	None	None	None	N	None	0	1.66772E-05	None	0	0	None	0	0	5.67985E-05	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	0.0665	benign	-0.657	Destabilizing	0.005	N	0.105	neutral	N	0.438271366	None	None	N
T/C	0.3051	likely_benign	0.3448	ambiguous	-0.498	Destabilizing	0.993	D	0.385	neutral	None	None	None	None	N
T/D	0.4425	ambiguous	0.4364	ambiguous	0.148	Stabilizing	0.915	D	0.393	neutral	None	None	None	None	N
T/E	0.3819	ambiguous	0.3756	ambiguous	0.172	Stabilizing	0.842	D	0.413	neutral	None	None	None	None	N
T/F	0.2754	likely_benign	0.2825	benign	-0.889	Destabilizing	0.974	D	0.455	neutral	None	None	None	None	N
T/G	0.156	likely_benign	0.1615	benign	-0.892	Destabilizing	0.728	D	0.423	neutral	None	None	None	None	N
T/H	0.2753	likely_benign	0.2824	benign	-0.941	Destabilizing	0.998	D	0.441	neutral	None	None	None	None	N
T/I	0.2031	likely_benign	0.2033	benign	-0.127	Destabilizing	0.934	D	0.42	neutral	N	0.475539976	None	None	N
T/K	0.2869	likely_benign	0.2769	benign	-0.393	Destabilizing	0.842	D	0.411	neutral	None	None	None	None	N
T/L	0.1092	likely_benign	0.1091	benign	-0.127	Destabilizing	0.842	D	0.387	neutral	None	None	None	None	N
T/M	0.0885	likely_benign	0.0919	benign	-0.216	Destabilizing	0.998	D	0.394	neutral	None	None	None	None	N
T/N	0.1104	likely_benign	0.1169	benign	-0.509	Destabilizing	0.966	D	0.401	neutral	N	0.499437255	None	None	N
T/P	0.1255	likely_benign	0.1066	benign	-0.272	Destabilizing	0.005	N	0.201	neutral	N	0.473133666	None	None	N
T/Q	0.2339	likely_benign	0.2376	benign	-0.531	Destabilizing	0.974	D	0.43	neutral	None	None	None	None	N
T/R	0.2604	likely_benign	0.2457	benign	-0.196	Destabilizing	0.974	D	0.423	neutral	None	None	None	None	N
T/S	0.0921	likely_benign	0.0978	benign	-0.789	Destabilizing	0.454	N	0.375	neutral	N	0.448931077	None	None	N
T/V	0.14	likely_benign	0.1413	benign	-0.272	Destabilizing	0.728	D	0.328	neutral	None	None	None	None	N
T/W	0.6096	likely_pathogenic	0.6222	pathogenic	-0.924	Destabilizing	0.998	D	0.564	neutral	None	None	None	None	N
T/Y	0.3276	likely_benign	0.3277	benign	-0.615	Destabilizing	0.991	D	0.453	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.