TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30404	91435;91436;91437	chr2:178551690;178551689;178551688	chr2:179416417;179416416;179416415
N2AB	28763	86512;86513;86514	chr2:178551690;178551689;178551688	chr2:179416417;179416416;179416415
N2A	27836	83731;83732;83733	chr2:178551690;178551689;178551688	chr2:179416417;179416416;179416415
N2B	21339	64240;64241;64242	chr2:178551690;178551689;178551688	chr2:179416417;179416416;179416415
Novex-1	21464	64615;64616;64617	chr2:178551690;178551689;178551688	chr2:179416417;179416416;179416415
Novex-2	21531	64816;64817;64818	chr2:178551690;178551689;178551688	chr2:179416417;179416416;179416415
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-109
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.7696
• Predicted PPI site: I

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
S/F	None	None	0.966	N	0.49	0.29	0.643794017197	gnomAD-4.0.0	1.59575E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86776E-06	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
S/A	0.0597	likely_benign	0.0591	benign	-0.388	Destabilizing	0.005	N	0.077	neutral	N	0.415853079	None	None	I
S/C	0.0983	likely_benign	0.0999	benign	-0.246	Destabilizing	0.997	D	0.367	neutral	N	0.47863694	None	None	I
S/D	0.3082	likely_benign	0.3668	ambiguous	-0.08	Destabilizing	0.728	D	0.255	neutral	None	None	None	None	I
S/E	0.3922	ambiguous	0.4176	ambiguous	-0.196	Destabilizing	0.842	D	0.259	neutral	None	None	None	None	I
S/F	0.1597	likely_benign	0.1768	benign	-1.118	Destabilizing	0.966	D	0.49	neutral	N	0.472053574	None	None	I
S/G	0.0855	likely_benign	0.0939	benign	-0.439	Destabilizing	0.525	D	0.335	neutral	None	None	None	None	I
S/H	0.2591	likely_benign	0.2895	benign	-0.945	Destabilizing	0.974	D	0.386	neutral	None	None	None	None	I
S/I	0.0915	likely_benign	0.0904	benign	-0.381	Destabilizing	0.949	D	0.49	neutral	None	None	None	None	I
S/K	0.4466	ambiguous	0.4934	ambiguous	-0.369	Destabilizing	0.067	N	0.159	neutral	None	None	None	None	I
S/L	0.0649	likely_benign	0.0654	benign	-0.381	Destabilizing	0.728	D	0.497	neutral	None	None	None	None	I
S/M	0.1338	likely_benign	0.1242	benign	-0.004	Destabilizing	0.991	D	0.376	neutral	None	None	None	None	I
S/N	0.096	likely_benign	0.1073	benign	-0.11	Destabilizing	0.007	N	0.067	neutral	None	None	None	None	I
S/P	0.1802	likely_benign	0.2783	benign	-0.359	Destabilizing	0.966	D	0.41	neutral	N	0.459414642	None	None	I
S/Q	0.3454	ambiguous	0.3652	ambiguous	-0.438	Destabilizing	0.949	D	0.297	neutral	None	None	None	None	I
S/R	0.3942	ambiguous	0.4456	ambiguous	-0.116	Destabilizing	0.728	D	0.451	neutral	None	None	None	None	I
S/T	0.0699	likely_benign	0.0701	benign	-0.234	Destabilizing	0.051	N	0.109	neutral	N	0.478421691	None	None	I
S/V	0.1088	likely_benign	0.1067	benign	-0.359	Destabilizing	0.728	D	0.505	neutral	None	None	None	None	I
S/W	0.3147	likely_benign	0.3552	ambiguous	-1.116	Destabilizing	0.998	D	0.548	neutral	None	None	None	None	I
S/Y	0.152	likely_benign	0.1708	benign	-0.835	Destabilizing	0.989	D	0.488	neutral	N	0.489993245	None	None	I

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.