TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15598	47017;47018;47019	chr2:178618758;178618757;178618756	chr2:179483485;179483484;179483483
N2AB	13957	42094;42095;42096	chr2:178618758;178618757;178618756	chr2:179483485;179483484;179483483
N2A	13030	39313;39314;39315	chr2:178618758;178618757;178618756	chr2:179483485;179483484;179483483
N2B	6533	19822;19823;19824	chr2:178618758;178618757;178618756	chr2:179483485;179483484;179483483
Novex-1	6658	20197;20198;20199	chr2:178618758;178618757;178618756	chr2:179483485;179483484;179483483
Novex-2	6725	20398;20399;20400	chr2:178618758;178618757;178618756	chr2:179483485;179483484;179483483
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-108
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.6452
• 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/D	rs371987003	None	0.996	N	0.485	0.166	0.440810947182	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.95E-05	0	0
E/D	rs371987003	None	0.996	N	0.485	0.166	0.440810947182	gnomAD-4.0.0	9.92776E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.35733E-05	0	0
E/K	None	None	0.992	N	0.541	0.335	0.429435026966	gnomAD-4.0.0	1.59583E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43419E-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
E/A	0.1189	likely_benign	0.1373	benign	-0.401	Destabilizing	0.996	D	0.633	neutral	N	0.509584452	None	None	N
E/C	0.7601	likely_pathogenic	0.8258	pathogenic	-0.106	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/D	0.1159	likely_benign	0.1456	benign	-0.457	Destabilizing	0.996	D	0.485	neutral	N	0.508507846	None	None	N
E/F	0.5489	ambiguous	0.6118	pathogenic	-0.314	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/G	0.1664	likely_benign	0.1908	benign	-0.628	Destabilizing	0.999	D	0.696	prob.neutral	N	0.51288252	None	None	N
E/H	0.305	likely_benign	0.3727	ambiguous	-0.32	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/I	0.2011	likely_benign	0.2398	benign	0.171	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/K	0.0925	likely_benign	0.1063	benign	-0.052	Destabilizing	0.992	D	0.541	neutral	N	0.506955764	None	None	N
E/L	0.2627	likely_benign	0.3222	benign	0.171	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
E/M	0.3161	likely_benign	0.3781	ambiguous	0.313	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/N	0.1586	likely_benign	0.1959	benign	-0.187	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/P	0.699	likely_pathogenic	0.708	pathogenic	0.001	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.1083	likely_benign	0.1261	benign	-0.15	Destabilizing	0.957	D	0.295	neutral	N	0.51275641	None	None	N
E/R	0.1748	likely_benign	0.1999	benign	0.145	Stabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
E/S	0.1384	likely_benign	0.1617	benign	-0.408	Destabilizing	0.997	D	0.619	neutral	None	None	None	None	N
E/T	0.1276	likely_benign	0.1406	benign	-0.239	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/V	0.128	likely_benign	0.1512	benign	0.001	Stabilizing	0.999	D	0.775	deleterious	N	0.51597344	None	None	N
E/W	0.7898	likely_pathogenic	0.8459	pathogenic	-0.208	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Y	0.4736	ambiguous	0.565	pathogenic	-0.101	Destabilizing	1.0	D	0.793	deleterious	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.