TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21463	64612;64613;64614	chr2:178586514;178586513;178586512	chr2:179451241;179451240;179451239
N2AB	19822	59689;59690;59691	chr2:178586514;178586513;178586512	chr2:179451241;179451240;179451239
N2A	18895	56908;56909;56910	chr2:178586514;178586513;178586512	chr2:179451241;179451240;179451239
N2B	12398	37417;37418;37419	chr2:178586514;178586513;178586512	chr2:179451241;179451240;179451239
Novex-1	12523	37792;37793;37794	chr2:178586514;178586513;178586512	chr2:179451241;179451240;179451239
Novex-2	12590	37993;37994;37995	chr2:178586514;178586513;178586512	chr2:179451241;179451240;179451239
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: Fn3-43
• Domain position: 98
• Structural Position: 132
• Q(SASA): 1.026
• 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	rs1214364121	0.673	0.856	N	0.653	0.258	0.311079019809	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	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	0.6603	likely_pathogenic	0.5199	ambiguous	-0.187	Destabilizing	0.748	D	0.637	neutral	N	0.504464647	None	None	N
E/C	0.9884	likely_pathogenic	0.9805	pathogenic	-0.136	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
E/D	0.2384	likely_benign	0.1912	benign	-0.265	Destabilizing	0.856	D	0.583	neutral	N	0.443954905	None	None	N
E/F	0.9885	likely_pathogenic	0.9761	pathogenic	-0.116	Destabilizing	0.982	D	0.681	prob.neutral	None	None	None	None	N
E/G	0.6626	likely_pathogenic	0.5255	ambiguous	-0.352	Destabilizing	0.954	D	0.434	neutral	N	0.492894805	None	None	N
E/H	0.9574	likely_pathogenic	0.9149	pathogenic	0.308	Stabilizing	0.998	D	0.642	neutral	None	None	None	None	N
E/I	0.9149	likely_pathogenic	0.8431	pathogenic	0.201	Stabilizing	0.932	D	0.685	prob.delet.	None	None	None	None	N
E/K	0.8412	likely_pathogenic	0.7125	pathogenic	0.348	Stabilizing	0.856	D	0.653	prob.neutral	N	0.490866889	None	None	N
E/L	0.9089	likely_pathogenic	0.8353	pathogenic	0.201	Stabilizing	0.932	D	0.535	neutral	None	None	None	None	N
E/M	0.9344	likely_pathogenic	0.8774	pathogenic	0.096	Stabilizing	0.995	D	0.66	prob.neutral	None	None	None	None	N
E/N	0.7405	likely_pathogenic	0.6173	pathogenic	0.074	Stabilizing	0.965	D	0.659	prob.neutral	None	None	None	None	N
E/P	0.851	likely_pathogenic	0.8009	pathogenic	0.091	Stabilizing	0.982	D	0.641	neutral	None	None	None	None	N
E/Q	0.6415	likely_pathogenic	0.477	ambiguous	0.103	Stabilizing	0.977	D	0.571	neutral	N	0.498628797	None	None	N
E/R	0.9094	likely_pathogenic	0.8326	pathogenic	0.596	Stabilizing	0.965	D	0.666	prob.neutral	None	None	None	None	N
E/S	0.7483	likely_pathogenic	0.6168	pathogenic	-0.085	Destabilizing	0.797	D	0.637	neutral	None	None	None	None	N
E/T	0.8135	likely_pathogenic	0.6829	pathogenic	0.052	Stabilizing	0.024	N	0.459	neutral	None	None	None	None	N
E/V	0.7982	likely_pathogenic	0.6713	pathogenic	0.091	Stabilizing	0.912	D	0.443	neutral	N	0.51099906	None	None	N
E/W	0.9952	likely_pathogenic	0.9908	pathogenic	-0.012	Destabilizing	0.998	D	0.784	deleterious	None	None	None	None	N
E/Y	0.9671	likely_pathogenic	0.9343	pathogenic	0.117	Stabilizing	0.994	D	0.643	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.