TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15121	45586;45587;45588	chr2:178621357;178621356;178621355	chr2:179486084;179486083;179486082
N2AB	13480	40663;40664;40665	chr2:178621357;178621356;178621355	chr2:179486084;179486083;179486082
N2A	12553	37882;37883;37884	chr2:178621357;178621356;178621355	chr2:179486084;179486083;179486082
N2B	6056	18391;18392;18393	chr2:178621357;178621356;178621355	chr2:179486084;179486083;179486082
Novex-1	6181	18766;18767;18768	chr2:178621357;178621356;178621355	chr2:179486084;179486083;179486082
Novex-2	6248	18967;18968;18969	chr2:178621357;178621356;178621355	chr2:179486084;179486083;179486082
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: Ig-103
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5133
• 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/K	rs1264862895	0.317	0.998	N	0.51	0.37	0.367992661779	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	2.94E-05	None	0	0	None	0	None	0	0	0
E/K	rs1264862895	0.317	0.998	N	0.51	0.37	0.367992661779	gnomAD-4.0.0	4.79411E-06	None	None	None	None	N	None	0	6.93033E-05	None	0	0	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
E/A	0.3821	ambiguous	0.4181	ambiguous	-0.338	Destabilizing	0.998	D	0.553	neutral	D	0.534439674	None	None	N
E/C	0.9785	likely_pathogenic	0.9817	pathogenic	-0.343	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/D	0.3922	ambiguous	0.3649	ambiguous	-0.552	Destabilizing	0.998	D	0.429	neutral	N	0.513621709	None	None	N
E/F	0.9553	likely_pathogenic	0.9683	pathogenic	0.295	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
E/G	0.5095	ambiguous	0.5627	ambiguous	-0.625	Destabilizing	0.999	D	0.556	neutral	D	0.62062925	None	None	N
E/H	0.8415	likely_pathogenic	0.8662	pathogenic	0.613	Stabilizing	0.702	D	0.295	neutral	None	None	None	None	N
E/I	0.7384	likely_pathogenic	0.7887	pathogenic	0.419	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	N
E/K	0.4376	ambiguous	0.5088	ambiguous	0.246	Stabilizing	0.998	D	0.51	neutral	N	0.506516677	None	None	N
E/L	0.8306	likely_pathogenic	0.8611	pathogenic	0.419	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	N
E/M	0.8187	likely_pathogenic	0.8517	pathogenic	0.34	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
E/N	0.6372	likely_pathogenic	0.6464	pathogenic	-0.509	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
E/P	0.961	likely_pathogenic	0.9475	pathogenic	0.188	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	N
E/Q	0.307	likely_benign	0.3552	ambiguous	-0.371	Destabilizing	0.999	D	0.594	neutral	N	0.509651256	None	None	N
E/R	0.6226	likely_pathogenic	0.6961	pathogenic	0.648	Stabilizing	1.0	D	0.618	neutral	None	None	None	None	N
E/S	0.4694	ambiguous	0.5114	ambiguous	-0.652	Destabilizing	0.998	D	0.553	neutral	None	None	None	None	N
E/T	0.49	ambiguous	0.5355	ambiguous	-0.39	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
E/V	0.4768	ambiguous	0.5517	ambiguous	0.188	Stabilizing	1.0	D	0.629	neutral	N	0.503429264	None	None	N
E/W	0.9911	likely_pathogenic	0.9932	pathogenic	0.575	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/Y	0.9251	likely_pathogenic	0.9393	pathogenic	0.584	Stabilizing	0.999	D	0.621	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.