TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6989	21190;21191;21192	chr2:178724410;178724409;178724408	chr2:179589137;179589136;179589135
N2AB	6672	20239;20240;20241	chr2:178724410;178724409;178724408	chr2:179589137;179589136;179589135
N2A	5745	17458;17459;17460	chr2:178724410;178724409;178724408	chr2:179589137;179589136;179589135
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-54
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.643
• 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/S	rs1228987960	-0.135	0.159	N	0.084	0.07	0.149567049428	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/S	rs1228987960	-0.135	0.159	N	0.084	0.07	0.149567049428	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/S	rs1228987960	-0.135	0.159	N	0.084	0.07	0.149567049428	gnomAD-4.0.0	6.57333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47059E-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	0.0732	likely_benign	0.071	benign	-0.463	Destabilizing	0.704	D	0.247	neutral	N	0.483649444	None	None	N
T/C	0.4051	ambiguous	0.4065	ambiguous	-0.509	Destabilizing	0.999	D	0.359	neutral	None	None	None	None	N
T/D	0.2517	likely_benign	0.2404	benign	0.456	Stabilizing	0.939	D	0.348	neutral	None	None	None	None	N
T/E	0.1811	likely_benign	0.1682	benign	0.42	Stabilizing	0.939	D	0.345	neutral	None	None	None	None	N
T/F	0.163	likely_benign	0.1547	benign	-1.029	Destabilizing	0.991	D	0.403	neutral	None	None	None	None	N
T/G	0.1955	likely_benign	0.1829	benign	-0.586	Destabilizing	0.939	D	0.358	neutral	None	None	None	None	N
T/H	0.1628	likely_benign	0.1632	benign	-0.633	Destabilizing	0.999	D	0.393	neutral	None	None	None	None	N
T/I	0.1239	likely_benign	0.1115	benign	-0.252	Destabilizing	0.134	N	0.18	neutral	N	0.491770282	None	None	N
T/K	0.1131	likely_benign	0.1123	benign	-0.178	Destabilizing	0.939	D	0.344	neutral	None	None	None	None	N
T/L	0.0784	likely_benign	0.0755	benign	-0.252	Destabilizing	0.759	D	0.313	neutral	None	None	None	None	N
T/M	0.085	likely_benign	0.0839	benign	-0.411	Destabilizing	0.991	D	0.367	neutral	None	None	None	None	N
T/N	0.0992	likely_benign	0.0933	benign	-0.199	Destabilizing	0.92	D	0.311	neutral	N	0.476587399	None	None	N
T/P	0.0805	likely_benign	0.085	benign	-0.295	Destabilizing	0.988	D	0.367	neutral	N	0.455329479	None	None	N
T/Q	0.1312	likely_benign	0.1317	benign	-0.27	Destabilizing	0.991	D	0.379	neutral	None	None	None	None	N
T/R	0.0943	likely_benign	0.1009	benign	0.049	Stabilizing	0.991	D	0.378	neutral	None	None	None	None	N
T/S	0.0902	likely_benign	0.0849	benign	-0.448	Destabilizing	0.159	N	0.084	neutral	N	0.458348355	None	None	N
T/V	0.1109	likely_benign	0.0991	benign	-0.295	Destabilizing	0.17	N	0.113	neutral	None	None	None	None	N
T/W	0.4443	ambiguous	0.437	ambiguous	-1.088	Destabilizing	0.999	D	0.455	neutral	None	None	None	None	N
T/Y	0.1877	likely_benign	0.1821	benign	-0.757	Destabilizing	0.997	D	0.41	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.