TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5177	15754;15755;15756	chr2:178733860;178733859;178733858	chr2:179598587;179598586;179598585
N2AB	4860	14803;14804;14805	chr2:178733860;178733859;178733858	chr2:179598587;179598586;179598585
N2A	3933	12022;12023;12024	chr2:178733860;178733859;178733858	chr2:179598587;179598586;179598585
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-35
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3871
• 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
L/W	rs1205797095	None	0.612	D	0.49	0.354	0.810717827077	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.92678E-04	None	0	0	0	0	0
L/W	rs1205797095	None	0.612	D	0.49	0.354	0.810717827077	gnomAD-4.0.0	6.5716E-06	None	None	None	None	I	None	0	0	None	0	1.92678E-04	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
L/A	0.0865	likely_benign	0.1082	benign	-1.363	Destabilizing	None	N	0.155	neutral	None	None	None	None	I
L/C	0.1125	likely_benign	0.137	benign	-0.878	Destabilizing	0.628	D	0.47	neutral	None	None	None	None	I
L/D	0.2398	likely_benign	0.3268	benign	-0.764	Destabilizing	0.136	N	0.599	neutral	None	None	None	None	I
L/E	0.1565	likely_benign	0.2049	benign	-0.747	Destabilizing	0.136	N	0.552	neutral	None	None	None	None	I
L/F	0.0382	likely_benign	0.0433	benign	-0.813	Destabilizing	None	N	0.073	neutral	D	0.554732472	None	None	I
L/G	0.206	likely_benign	0.2716	benign	-1.693	Destabilizing	0.031	N	0.406	neutral	None	None	None	None	I
L/H	0.0703	likely_benign	0.0899	benign	-0.908	Destabilizing	0.356	N	0.507	neutral	None	None	None	None	I
L/I	0.0432	likely_benign	0.0459	benign	-0.535	Destabilizing	None	N	0.095	neutral	None	None	None	None	I
L/K	0.1234	likely_benign	0.1604	benign	-1.002	Destabilizing	0.072	N	0.54	neutral	None	None	None	None	I
L/M	0.0639	likely_benign	0.0682	benign	-0.517	Destabilizing	0.171	N	0.428	neutral	N	0.511970565	None	None	I
L/N	0.1208	likely_benign	0.1612	benign	-0.831	Destabilizing	0.136	N	0.607	neutral	None	None	None	None	I
L/P	0.5899	likely_pathogenic	0.6622	pathogenic	-0.779	Destabilizing	0.136	N	0.605	neutral	None	None	None	None	I
L/Q	0.0725	likely_benign	0.0908	benign	-0.945	Destabilizing	0.628	D	0.609	neutral	None	None	None	None	I
L/R	0.0852	likely_benign	0.1086	benign	-0.489	Destabilizing	0.136	N	0.629	neutral	None	None	None	None	I
L/S	0.0868	likely_benign	0.1165	benign	-1.428	Destabilizing	0.012	N	0.369	neutral	N	0.515696288	None	None	I
L/T	0.0704	likely_benign	0.0902	benign	-1.287	Destabilizing	None	N	0.157	neutral	None	None	None	None	I
L/V	0.0411	likely_benign	0.0446	benign	-0.779	Destabilizing	None	N	0.067	neutral	N	0.443318264	None	None	I
L/W	0.092	likely_benign	0.1047	benign	-0.906	Destabilizing	0.612	D	0.49	neutral	D	0.67809784	None	None	I
L/Y	0.0781	likely_benign	0.0956	benign	-0.678	Destabilizing	0.038	N	0.493	neutral	None	None	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.