TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32025	96298;96299;96300	chr2:178544071;178544070;178544069	chr2:179408798;179408797;179408796
N2AB	30384	91375;91376;91377	chr2:178544071;178544070;178544069	chr2:179408798;179408797;179408796
N2A	29457	88594;88595;88596	chr2:178544071;178544070;178544069	chr2:179408798;179408797;179408796
N2B	22960	69103;69104;69105	chr2:178544071;178544070;178544069	chr2:179408798;179408797;179408796
Novex-1	23085	69478;69479;69480	chr2:178544071;178544070;178544069	chr2:179408798;179408797;179408796
Novex-2	23152	69679;69680;69681	chr2:178544071;178544070;178544069	chr2:179408798;179408797;179408796
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: Ig-153
• Domain position: 9
• Structural Position: 14
• Q(SASA): 0.4531
• 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	rs1259754105	None	None	N	0.194	0.1	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1259754105	None	None	N	0.194	0.1	None	gnomAD-4.0.0	3.84548E-06	None	None	None	None	N	None	3.38387E-05	0	None	0	0	None	0	0	0	1.34073E-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
T/A	0.0956	likely_benign	0.101	benign	-0.648	Destabilizing	0.027	N	0.295	neutral	N	0.484958768	None	None	N
T/C	0.2797	likely_benign	0.3069	benign	-0.425	Destabilizing	0.001	N	0.235	neutral	None	None	None	None	N
T/D	0.6905	likely_pathogenic	0.6891	pathogenic	0.368	Stabilizing	0.555	D	0.385	neutral	None	None	None	None	N
T/E	0.5789	likely_pathogenic	0.5852	pathogenic	0.402	Stabilizing	0.555	D	0.378	neutral	None	None	None	None	N
T/F	0.2834	likely_benign	0.3054	benign	-0.709	Destabilizing	0.38	N	0.371	neutral	None	None	None	None	N
T/G	0.3356	likely_benign	0.3711	ambiguous	-0.917	Destabilizing	0.262	N	0.361	neutral	None	None	None	None	N
T/H	0.3849	ambiguous	0.3891	ambiguous	-1.02	Destabilizing	0.935	D	0.367	neutral	None	None	None	None	N
T/I	0.1119	likely_benign	0.1209	benign	-0.019	Destabilizing	None	N	0.194	neutral	N	0.475686109	None	None	N
T/K	0.4729	ambiguous	0.4693	ambiguous	-0.354	Destabilizing	0.555	D	0.381	neutral	None	None	None	None	N
T/L	0.1006	likely_benign	0.1082	benign	-0.019	Destabilizing	0.012	N	0.344	neutral	None	None	None	None	N
T/M	0.0835	likely_benign	0.0877	benign	-0.053	Destabilizing	0.38	N	0.382	neutral	None	None	None	None	N
T/N	0.1498	likely_benign	0.1585	benign	-0.423	Destabilizing	0.741	D	0.333	neutral	N	0.52032232	None	None	N
T/P	0.2375	likely_benign	0.2484	benign	-0.196	Destabilizing	0.741	D	0.395	neutral	N	0.512510452	None	None	N
T/Q	0.3626	ambiguous	0.3677	ambiguous	-0.447	Destabilizing	0.791	D	0.379	neutral	None	None	None	None	N
T/R	0.4179	ambiguous	0.4207	ambiguous	-0.234	Destabilizing	0.555	D	0.383	neutral	None	None	None	None	N
T/S	0.1373	likely_benign	0.151	benign	-0.766	Destabilizing	0.211	N	0.25	neutral	N	0.499696332	None	None	N
T/V	0.0929	likely_benign	0.1003	benign	-0.196	Destabilizing	0.001	N	0.119	neutral	None	None	None	None	N
T/W	0.6944	likely_pathogenic	0.7045	pathogenic	-0.696	Destabilizing	0.935	D	0.419	neutral	None	None	None	None	N
T/Y	0.3423	ambiguous	0.3571	ambiguous	-0.407	Destabilizing	0.555	D	0.378	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.