TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18818	56677;56678;56679	chr2:178599341;178599340;178599339	chr2:179464068;179464067;179464066
N2AB	17177	51754;51755;51756	chr2:178599341;178599340;178599339	chr2:179464068;179464067;179464066
N2A	16250	48973;48974;48975	chr2:178599341;178599340;178599339	chr2:179464068;179464067;179464066
N2B	9753	29482;29483;29484	chr2:178599341;178599340;178599339	chr2:179464068;179464067;179464066
Novex-1	9878	29857;29858;29859	chr2:178599341;178599340;178599339	chr2:179464068;179464067;179464066
Novex-2	9945	30058;30059;30060	chr2:178599341;178599340;178599339	chr2:179464068;179464067;179464066
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-24
• Domain position: 35
• Structural Position: 36
• Q(SASA): 0.5418
• 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
T/K	rs945270235	-0.395	1.0	N	0.823	0.447	0.520110530135	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	0	2.97E-05	None	0	0	None	0	None	0	0	0
T/K	rs945270235	-0.395	1.0	N	0.823	0.447	0.520110530135	gnomAD-4.0.0	1.60193E-06	None	None	None	None	I	None	0	2.32515E-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	0.2672	likely_benign	0.2523	benign	-0.7	Destabilizing	0.999	D	0.549	neutral	N	0.488324632	None	None	I
T/C	0.7623	likely_pathogenic	0.746	pathogenic	-0.458	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
T/D	0.7453	likely_pathogenic	0.7051	pathogenic	-0.581	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
T/E	0.6439	likely_pathogenic	0.59	pathogenic	-0.604	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
T/F	0.6787	likely_pathogenic	0.6108	pathogenic	-0.862	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
T/G	0.5523	ambiguous	0.505	ambiguous	-0.931	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
T/H	0.64	likely_pathogenic	0.5782	pathogenic	-1.271	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
T/I	0.4829	ambiguous	0.4252	ambiguous	-0.181	Destabilizing	1.0	D	0.815	deleterious	N	0.498127746	None	None	I
T/K	0.5852	likely_pathogenic	0.5253	ambiguous	-0.825	Destabilizing	1.0	D	0.823	deleterious	N	0.47218216	None	None	I
T/L	0.2486	likely_benign	0.2164	benign	-0.181	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
T/M	0.1889	likely_benign	0.1705	benign	0.209	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
T/N	0.3064	likely_benign	0.2755	benign	-0.754	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
T/P	0.8349	likely_pathogenic	0.7961	pathogenic	-0.322	Destabilizing	1.0	D	0.808	deleterious	N	0.516597104	None	None	I
T/Q	0.5113	ambiguous	0.4552	ambiguous	-0.995	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
T/R	0.5288	ambiguous	0.4727	ambiguous	-0.501	Destabilizing	1.0	D	0.805	deleterious	N	0.474259301	None	None	I
T/S	0.1948	likely_benign	0.1849	benign	-0.949	Destabilizing	0.999	D	0.564	neutral	N	0.516481434	None	None	I
T/V	0.3931	ambiguous	0.3527	ambiguous	-0.322	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
T/W	0.8854	likely_pathogenic	0.8507	pathogenic	-0.812	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
T/Y	0.7341	likely_pathogenic	0.6655	pathogenic	-0.58	Destabilizing	1.0	D	0.815	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.