TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9254	27985;27986;27987	chr2:178712070;178712069;178712068	chr2:179576797;179576796;179576795
N2AB	8937	27034;27035;27036	chr2:178712070;178712069;178712068	chr2:179576797;179576796;179576795
N2A	8010	24253;24254;24255	chr2:178712070;178712069;178712068	chr2:179576797;179576796;179576795
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-78
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.5449
• 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
H/N	rs1191894899	0.17	0.642	N	0.211	0.186	0.26169431596	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/N	rs1191894899	0.17	0.642	N	0.211	0.186	0.26169431596	gnomAD-4.0.0	3.18256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86574E-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
H/A	0.3096	likely_benign	0.3781	ambiguous	0.652	Stabilizing	0.495	N	0.305	neutral	None	None	None	None	N
H/C	0.2291	likely_benign	0.2771	benign	1.193	Stabilizing	0.995	D	0.334	neutral	None	None	None	None	N
H/D	0.2883	likely_benign	0.3617	ambiguous	0.241	Stabilizing	0.002	N	0.171	neutral	N	0.439954595	None	None	N
H/E	0.3332	likely_benign	0.3936	ambiguous	0.27	Stabilizing	0.004	N	0.098	neutral	None	None	None	None	N
H/F	0.2201	likely_benign	0.2368	benign	1.286	Stabilizing	0.007	N	0.225	neutral	None	None	None	None	N
H/G	0.4243	ambiguous	0.5027	ambiguous	0.354	Stabilizing	0.665	D	0.355	neutral	None	None	None	None	N
H/I	0.2093	likely_benign	0.2452	benign	1.413	Stabilizing	0.543	D	0.419	neutral	None	None	None	None	N
H/K	0.3579	ambiguous	0.4047	ambiguous	0.715	Stabilizing	0.495	N	0.321	neutral	None	None	None	None	N
H/L	0.1128	likely_benign	0.1323	benign	1.413	Stabilizing	0.002	N	0.256	neutral	N	0.421792909	None	None	N
H/M	0.4195	ambiguous	0.4416	ambiguous	1.115	Stabilizing	0.893	D	0.354	neutral	None	None	None	None	N
H/N	0.1077	likely_benign	0.1244	benign	0.796	Stabilizing	0.642	D	0.211	neutral	N	0.462908813	None	None	N
H/P	0.6322	likely_pathogenic	0.7751	pathogenic	1.186	Stabilizing	0.917	D	0.412	neutral	N	0.497098744	None	None	N
H/Q	0.1979	likely_benign	0.2277	benign	0.901	Stabilizing	0.642	D	0.197	neutral	N	0.42692937	None	None	N
H/R	0.1626	likely_benign	0.2093	benign	-0.019	Destabilizing	0.642	D	0.191	neutral	N	0.39658782	None	None	N
H/S	0.2323	likely_benign	0.2693	benign	0.937	Stabilizing	0.495	N	0.305	neutral	None	None	None	None	N
H/T	0.247	likely_benign	0.291	benign	1.066	Stabilizing	0.828	D	0.393	neutral	None	None	None	None	N
H/V	0.191	likely_benign	0.2183	benign	1.186	Stabilizing	0.329	N	0.399	neutral	None	None	None	None	N
H/W	0.3866	ambiguous	0.4399	ambiguous	1.228	Stabilizing	0.995	D	0.321	neutral	None	None	None	None	N
H/Y	0.0678	likely_benign	0.0766	benign	1.555	Stabilizing	0.473	N	0.233	neutral	N	0.4180806	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.