TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3294	10105;10106;10107	chr2:178764635;178764634;178764633	chr2:179629362;179629361;179629360
N2AB	3294	10105;10106;10107	chr2:178764635;178764634;178764633	chr2:179629362;179629361;179629360
N2A	3294	10105;10106;10107	chr2:178764635;178764634;178764633	chr2:179629362;179629361;179629360
N2B	3248	9967;9968;9969	chr2:178764635;178764634;178764633	chr2:179629362;179629361;179629360
Novex-1	3248	9967;9968;9969	chr2:178764635;178764634;178764633	chr2:179629362;179629361;179629360
Novex-2	3248	9967;9968;9969	chr2:178764635;178764634;178764633	chr2:179629362;179629361;179629360
Novex-3	3294	10105;10106;10107	chr2:178764635;178764634;178764633	chr2:179629362;179629361;179629360

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-23
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1707
• 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
Y/C	None	None	1.0	N	0.753	0.575	0.636119361578	gnomAD-4.0.0	2.40066E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-06	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
Y/A	0.9171	likely_pathogenic	0.9611	pathogenic	-3.075	Highly Destabilizing	0.985	D	0.682	prob.neutral	None	None	None	None	N
Y/C	0.5206	ambiguous	0.7488	pathogenic	-1.836	Destabilizing	1.0	D	0.753	deleterious	N	0.469289594	None	None	N
Y/D	0.9423	likely_pathogenic	0.98	pathogenic	-3.181	Highly Destabilizing	0.994	D	0.739	prob.delet.	D	0.593101169	None	None	N
Y/E	0.9783	likely_pathogenic	0.9919	pathogenic	-3.021	Highly Destabilizing	0.97	D	0.697	prob.neutral	None	None	None	None	N
Y/F	0.2254	likely_benign	0.2579	benign	-1.098	Destabilizing	0.98	D	0.653	neutral	N	0.515047253	None	None	N
Y/G	0.9317	likely_pathogenic	0.969	pathogenic	-3.47	Highly Destabilizing	0.985	D	0.723	prob.delet.	None	None	None	None	N
Y/H	0.5086	ambiguous	0.6871	pathogenic	-1.983	Destabilizing	0.071	N	0.457	neutral	N	0.449172325	None	None	N
Y/I	0.8972	likely_pathogenic	0.9558	pathogenic	-1.786	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
Y/K	0.9685	likely_pathogenic	0.9888	pathogenic	-2.143	Highly Destabilizing	0.991	D	0.713	prob.delet.	None	None	None	None	N
Y/L	0.87	likely_pathogenic	0.9366	pathogenic	-1.786	Destabilizing	0.985	D	0.665	neutral	None	None	None	None	N
Y/M	0.9035	likely_pathogenic	0.954	pathogenic	-1.487	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
Y/N	0.6837	likely_pathogenic	0.8583	pathogenic	-2.768	Highly Destabilizing	0.989	D	0.711	prob.delet.	D	0.568899777	None	None	N
Y/P	0.9971	likely_pathogenic	0.9992	pathogenic	-2.226	Highly Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
Y/Q	0.9429	likely_pathogenic	0.9804	pathogenic	-2.609	Highly Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
Y/R	0.9351	likely_pathogenic	0.9751	pathogenic	-1.733	Destabilizing	0.991	D	0.729	prob.delet.	None	None	None	None	N
Y/S	0.8021	likely_pathogenic	0.9168	pathogenic	-3.144	Highly Destabilizing	0.98	D	0.705	prob.neutral	N	0.511760013	None	None	N
Y/T	0.9149	likely_pathogenic	0.9686	pathogenic	-2.874	Highly Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	N
Y/V	0.8137	likely_pathogenic	0.9078	pathogenic	-2.226	Highly Destabilizing	0.995	D	0.684	prob.neutral	None	None	None	None	N
Y/W	0.7696	likely_pathogenic	0.8329	pathogenic	-0.536	Destabilizing	1.0	D	0.677	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.