TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23784	71575;71576;71577	chr2:178574782;178574781;178574780	chr2:179439509;179439508;179439507
N2AB	22143	66652;66653;66654	chr2:178574782;178574781;178574780	chr2:179439509;179439508;179439507
N2A	21216	63871;63872;63873	chr2:178574782;178574781;178574780	chr2:179439509;179439508;179439507
N2B	14719	44380;44381;44382	chr2:178574782;178574781;178574780	chr2:179439509;179439508;179439507
Novex-1	14844	44755;44756;44757	chr2:178574782;178574781;178574780	chr2:179439509;179439508;179439507
Novex-2	14911	44956;44957;44958	chr2:178574782;178574781;178574780	chr2:179439509;179439508;179439507
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-60
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.2587
• 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	None	None	1.0	N	0.743	0.481	0.449956787536	gnomAD-4.0.0	1.59524E-06	None	None	None	None	N	None	0	0	None	0	2.78211E-05	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
T/A	0.1975	likely_benign	0.2272	benign	-0.897	Destabilizing	0.999	D	0.547	neutral	N	0.481852944	None	None	N
T/C	0.3645	ambiguous	0.4166	ambiguous	-0.436	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
T/D	0.7932	likely_pathogenic	0.8413	pathogenic	-0.345	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
T/E	0.7033	likely_pathogenic	0.7672	pathogenic	-0.203	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
T/F	0.8334	likely_pathogenic	0.9035	pathogenic	-0.812	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
T/G	0.4085	ambiguous	0.443	ambiguous	-1.266	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/H	0.5359	ambiguous	0.5946	pathogenic	-1.34	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/I	0.7979	likely_pathogenic	0.8662	pathogenic	0.042	Stabilizing	1.0	D	0.743	deleterious	N	0.481599454	None	None	N
T/K	0.3877	ambiguous	0.4293	ambiguous	-0.221	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
T/L	0.2727	likely_benign	0.4049	ambiguous	0.042	Stabilizing	0.999	D	0.631	neutral	None	None	None	None	N
T/M	0.1696	likely_benign	0.2343	benign	0.022	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/N	0.1779	likely_benign	0.213	benign	-0.687	Destabilizing	1.0	D	0.689	prob.neutral	N	0.512382336	None	None	N
T/P	0.1805	likely_benign	0.163	benign	-0.238	Destabilizing	1.0	D	0.75	deleterious	N	0.466148614	None	None	N
T/Q	0.3683	ambiguous	0.4187	ambiguous	-0.535	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/R	0.3489	ambiguous	0.3624	ambiguous	-0.328	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
T/S	0.2417	likely_benign	0.2688	benign	-1.021	Destabilizing	0.999	D	0.523	neutral	N	0.490217552	None	None	N
T/V	0.5385	ambiguous	0.6244	pathogenic	-0.238	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
T/W	0.9561	likely_pathogenic	0.9678	pathogenic	-0.881	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
T/Y	0.747	likely_pathogenic	0.8223	pathogenic	-0.51	Destabilizing	1.0	D	0.796	deleterious	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.