TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7909	23950;23951;23952	chr2:178719767;178719766;178719765	chr2:179584494;179584493;179584492
N2AB	7592	22999;23000;23001	chr2:178719767;178719766;178719765	chr2:179584494;179584493;179584492
N2A	6665	20218;20219;20220	chr2:178719767;178719766;178719765	chr2:179584494;179584493;179584492
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-64
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5119
• Predicted PPI site: I

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/G	None	None	0.994	D	0.646	0.592	0.610906440916	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
E/Q	rs1161435142	-0.388	0.998	D	0.65	0.474	0.436993770938	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/Q	rs1161435142	-0.388	0.998	D	0.65	0.474	0.436993770938	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs1161435142	-0.388	0.998	D	0.65	0.474	0.436993770938	gnomAD-4.0.0	2.23122E-05	None	None	None	None	I	None	0	0	None	3.37861E-05	0	None	0	0	2.8822E-05	0	1.60159E-05

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	0.3735	ambiguous	0.4492	ambiguous	-0.849	Destabilizing	0.994	D	0.642	neutral	N	0.510611121	None	None	I
E/C	0.9525	likely_pathogenic	0.9689	pathogenic	-0.411	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/D	0.3481	ambiguous	0.4163	ambiguous	-1.118	Destabilizing	0.104	N	0.229	neutral	N	0.504027755	None	None	I
E/F	0.9012	likely_pathogenic	0.9284	pathogenic	-0.405	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
E/G	0.5004	ambiguous	0.5757	pathogenic	-1.198	Destabilizing	0.994	D	0.646	neutral	D	0.529084224	None	None	I
E/H	0.6827	likely_pathogenic	0.7609	pathogenic	-0.637	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
E/I	0.6322	likely_pathogenic	0.7188	pathogenic	0.097	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
E/K	0.4101	ambiguous	0.5325	ambiguous	-0.529	Destabilizing	0.994	D	0.555	neutral	N	0.49116374	None	None	I
E/L	0.6837	likely_pathogenic	0.779	pathogenic	0.097	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
E/M	0.7271	likely_pathogenic	0.798	pathogenic	0.543	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
E/N	0.5765	likely_pathogenic	0.6828	pathogenic	-1.004	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	I
E/P	0.9763	likely_pathogenic	0.9809	pathogenic	-0.197	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
E/Q	0.2042	likely_benign	0.2557	benign	-0.884	Destabilizing	0.998	D	0.65	neutral	D	0.53423298	None	None	I
E/R	0.5537	ambiguous	0.6543	pathogenic	-0.265	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	I
E/S	0.4097	ambiguous	0.4907	ambiguous	-1.284	Destabilizing	0.992	D	0.559	neutral	None	None	None	None	I
E/T	0.4215	ambiguous	0.5275	ambiguous	-0.995	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
E/V	0.4132	ambiguous	0.5008	ambiguous	-0.197	Destabilizing	0.999	D	0.765	deleterious	N	0.508270944	None	None	I
E/W	0.9687	likely_pathogenic	0.9776	pathogenic	-0.173	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
E/Y	0.8468	likely_pathogenic	0.8877	pathogenic	-0.155	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I

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.