TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14942	45049;45050;45051	chr2:178622759;178622758;178622757	chr2:179487486;179487485;179487484
N2AB	13301	40126;40127;40128	chr2:178622759;178622758;178622757	chr2:179487486;179487485;179487484
N2A	12374	37345;37346;37347	chr2:178622759;178622758;178622757	chr2:179487486;179487485;179487484
N2B	5877	17854;17855;17856	chr2:178622759;178622758;178622757	chr2:179487486;179487485;179487484
Novex-1	6002	18229;18230;18231	chr2:178622759;178622758;178622757	chr2:179487486;179487485;179487484
Novex-2	6069	18430;18431;18432	chr2:178622759;178622758;178622757	chr2:179487486;179487485;179487484
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-101
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.3044
• 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
V/M	rs786205391	None	0.998	D	0.672	0.324	0.661726622693	gnomAD-4.0.0	6.90904E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.05525E-07	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
V/A	0.3965	ambiguous	0.3683	ambiguous	-1.299	Destabilizing	0.996	D	0.566	neutral	D	0.631594757	None	None	N
V/C	0.8979	likely_pathogenic	0.8841	pathogenic	-0.92	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
V/D	0.8098	likely_pathogenic	0.7808	pathogenic	-0.751	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
V/E	0.6639	likely_pathogenic	0.6339	pathogenic	-0.71	Destabilizing	1.0	D	0.659	neutral	D	0.676178714	None	None	N
V/F	0.4875	ambiguous	0.4389	ambiguous	-0.874	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
V/G	0.5773	likely_pathogenic	0.5581	ambiguous	-1.658	Destabilizing	1.0	D	0.705	prob.neutral	D	0.677675637	None	None	N
V/H	0.9276	likely_pathogenic	0.9198	pathogenic	-1.212	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
V/I	0.1122	likely_benign	0.1059	benign	-0.406	Destabilizing	0.971	D	0.52	neutral	None	None	None	None	N
V/K	0.831	likely_pathogenic	0.8143	pathogenic	-0.987	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
V/L	0.4104	ambiguous	0.3759	ambiguous	-0.406	Destabilizing	0.275	N	0.325	neutral	D	0.530107478	None	None	N
V/M	0.3506	ambiguous	0.3152	benign	-0.432	Destabilizing	0.998	D	0.672	neutral	D	0.635942745	None	None	N
V/N	0.7807	likely_pathogenic	0.7564	pathogenic	-0.824	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
V/P	0.8149	likely_pathogenic	0.8111	pathogenic	-0.667	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
V/Q	0.7759	likely_pathogenic	0.7604	pathogenic	-0.886	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
V/R	0.7639	likely_pathogenic	0.7462	pathogenic	-0.649	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
V/S	0.5922	likely_pathogenic	0.5623	ambiguous	-1.426	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
V/T	0.3519	ambiguous	0.3324	benign	-1.254	Destabilizing	0.997	D	0.565	neutral	None	None	None	None	N
V/W	0.9569	likely_pathogenic	0.9454	pathogenic	-1.087	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
V/Y	0.8629	likely_pathogenic	0.8468	pathogenic	-0.757	Destabilizing	1.0	D	0.685	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.