TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32625	98098;98099;98100	chr2:178540293;178540292;178540291	chr2:179405020;179405019;179405018
N2AB	30984	93175;93176;93177	chr2:178540293;178540292;178540291	chr2:179405020;179405019;179405018
N2A	30057	90394;90395;90396	chr2:178540293;178540292;178540291	chr2:179405020;179405019;179405018
N2B	23560	70903;70904;70905	chr2:178540293;178540292;178540291	chr2:179405020;179405019;179405018
Novex-1	23685	71278;71279;71280	chr2:178540293;178540292;178540291	chr2:179405020;179405019;179405018
Novex-2	23752	71479;71480;71481	chr2:178540293;178540292;178540291	chr2:179405020;179405019;179405018
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-126
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8224
• 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
E/G	None	None	1.0	N	0.636	0.449	0.394536629495	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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
E/A	0.119	likely_benign	0.1425	benign	-0.17	Destabilizing	0.999	D	0.656	neutral	N	0.434748271	None	None	N
E/C	0.7289	likely_pathogenic	0.7638	pathogenic	-0.05	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/D	0.1263	likely_benign	0.1318	benign	-0.28	Destabilizing	0.999	D	0.548	neutral	N	0.437327217	None	None	N
E/F	0.6398	likely_pathogenic	0.7125	pathogenic	-0.163	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/G	0.1539	likely_benign	0.1817	benign	-0.326	Destabilizing	1.0	D	0.636	neutral	N	0.49385529	None	None	N
E/H	0.3508	ambiguous	0.4403	ambiguous	0.234	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/I	0.2703	likely_benign	0.3138	benign	0.193	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/K	0.1045	likely_benign	0.1373	benign	0.41	Stabilizing	0.999	D	0.699	prob.neutral	N	0.431361249	None	None	N
E/L	0.272	likely_benign	0.3409	ambiguous	0.193	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/M	0.3646	ambiguous	0.42	ambiguous	0.125	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
E/N	0.2269	likely_benign	0.2633	benign	0.18	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/P	0.3517	ambiguous	0.4538	ambiguous	0.092	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/Q	0.1077	likely_benign	0.153	benign	0.191	Stabilizing	1.0	D	0.661	neutral	N	0.480944708	None	None	N
E/R	0.1706	likely_benign	0.2283	benign	0.619	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/S	0.1696	likely_benign	0.1979	benign	0.019	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
E/T	0.1718	likely_benign	0.1999	benign	0.147	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/V	0.1708	likely_benign	0.1975	benign	0.092	Stabilizing	1.0	D	0.709	prob.delet.	N	0.474826812	None	None	N
E/W	0.7627	likely_pathogenic	0.84	pathogenic	-0.074	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/Y	0.5127	ambiguous	0.5932	pathogenic	0.071	Stabilizing	1.0	D	0.688	prob.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.