TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9290	28093;28094;28095	chr2:178711962;178711961;178711960	chr2:179576689;179576688;179576687
N2AB	8973	27142;27143;27144	chr2:178711962;178711961;178711960	chr2:179576689;179576688;179576687
N2A	8046	24361;24362;24363	chr2:178711962;178711961;178711960	chr2:179576689;179576688;179576687
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-78
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1514
• 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
T/A	rs1256283190	None	0.004	N	0.263	0.105	0.12205267543	gnomAD-4.0.0	1.62297E-06	None	None	None	None	N	None	0	2.33634E-05	None	0	0	None	0	0	0	0	0
T/S	rs1196673354	-1.29	0.043	N	0.291	0.093	0.184867976434	gnomAD-2.1.1	4.14E-06	None	None	None	None	N	None	0	2.97E-05	None	0	0	None	0	None	0	0	0
T/S	rs1196673354	-1.29	0.043	N	0.291	0.093	0.184867976434	gnomAD-4.0.0	1.62302E-06	None	None	None	None	N	None	0	2.33754E-05	None	0	0	None	0	0	0	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
T/A	0.0565	likely_benign	0.0717	benign	-1.032	Destabilizing	0.004	N	0.263	neutral	N	0.399854625	None	None	N
T/C	0.2861	likely_benign	0.3906	ambiguous	-0.49	Destabilizing	0.992	D	0.748	deleterious	None	None	None	None	N
T/D	0.6637	likely_pathogenic	0.7994	pathogenic	-0.781	Destabilizing	0.816	D	0.776	deleterious	None	None	None	None	N
T/E	0.6849	likely_pathogenic	0.8269	pathogenic	-0.588	Destabilizing	0.816	D	0.763	deleterious	None	None	None	None	N
T/F	0.5252	ambiguous	0.7542	pathogenic	-0.674	Destabilizing	0.969	D	0.795	deleterious	None	None	None	None	N
T/G	0.2112	likely_benign	0.2697	benign	-1.454	Destabilizing	0.69	D	0.719	prob.delet.	None	None	None	None	N
T/H	0.5122	ambiguous	0.7197	pathogenic	-1.457	Destabilizing	0.997	D	0.769	deleterious	None	None	None	None	N
T/I	0.3201	likely_benign	0.5147	ambiguous	0.073	Stabilizing	0.922	D	0.793	deleterious	N	0.482531936	None	None	N
T/K	0.603	likely_pathogenic	0.7811	pathogenic	-0.223	Destabilizing	0.816	D	0.768	deleterious	None	None	None	None	N
T/L	0.1965	likely_benign	0.3775	ambiguous	0.073	Stabilizing	0.816	D	0.695	prob.neutral	None	None	None	None	N
T/M	0.1535	likely_benign	0.2866	benign	0.054	Stabilizing	0.997	D	0.759	deleterious	None	None	None	None	N
T/N	0.2609	likely_benign	0.3915	ambiguous	-0.818	Destabilizing	0.77	D	0.659	neutral	N	0.51559787	None	None	N
T/P	0.5948	likely_pathogenic	0.8357	pathogenic	-0.263	Destabilizing	0.96	D	0.791	deleterious	N	0.51585136	None	None	N
T/Q	0.5198	ambiguous	0.7073	pathogenic	-0.604	Destabilizing	0.969	D	0.799	deleterious	None	None	None	None	N
T/R	0.4579	ambiguous	0.676	pathogenic	-0.443	Destabilizing	0.94	D	0.796	deleterious	None	None	None	None	N
T/S	0.1072	likely_benign	0.1248	benign	-1.146	Destabilizing	0.043	N	0.291	neutral	N	0.469720142	None	None	N
T/V	0.1867	likely_benign	0.29	benign	-0.263	Destabilizing	0.69	D	0.6	neutral	None	None	None	None	N
T/W	0.8753	likely_pathogenic	0.9627	pathogenic	-0.761	Destabilizing	0.997	D	0.767	deleterious	None	None	None	None	N
T/Y	0.5416	ambiguous	0.7905	pathogenic	-0.388	Destabilizing	0.99	D	0.801	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.