TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4933	15022;15023;15024	chr2:178735649;178735648;178735647	chr2:179600376;179600375;179600374
N2AB	4616	14071;14072;14073	chr2:178735649;178735648;178735647	chr2:179600376;179600375;179600374
N2A	3689	11290;11291;11292	chr2:178735649;178735648;178735647	chr2:179600376;179600375;179600374
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-32
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.6018
• 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
D/Y	rs984284016	0.115	1.0	N	0.718	0.365	0.439445477881	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
D/Y	rs984284016	0.115	1.0	N	0.718	0.365	0.439445477881	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/Y	rs984284016	0.115	1.0	N	0.718	0.365	0.439445477881	gnomAD-4.0.0	6.57056E-06	None	None	None	None	N	None	2.41173E-05	0	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
D/A	0.2152	likely_benign	0.2935	benign	-0.307	Destabilizing	0.996	D	0.675	neutral	N	0.436631027	None	None	N
D/C	0.7072	likely_pathogenic	0.7973	pathogenic	-0.217	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
D/E	0.1818	likely_benign	0.212	benign	-0.289	Destabilizing	0.996	D	0.419	neutral	N	0.448741878	None	None	N
D/F	0.5588	ambiguous	0.6588	pathogenic	0.116	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
D/G	0.191	likely_benign	0.2629	benign	-0.579	Destabilizing	0.998	D	0.669	neutral	N	0.446411319	None	None	N
D/H	0.3901	ambiguous	0.5088	ambiguous	0.192	Stabilizing	1.0	D	0.696	prob.neutral	N	0.434250805	None	None	N
D/I	0.346	ambiguous	0.4466	ambiguous	0.386	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
D/K	0.5505	ambiguous	0.6782	pathogenic	0.059	Stabilizing	0.91	D	0.319	neutral	None	None	None	None	N
D/L	0.4459	ambiguous	0.5466	ambiguous	0.386	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
D/M	0.6362	likely_pathogenic	0.7359	pathogenic	0.429	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
D/N	0.1265	likely_benign	0.1563	benign	-0.399	Destabilizing	0.999	D	0.651	neutral	N	0.444179912	None	None	N
D/P	0.7537	likely_pathogenic	0.8284	pathogenic	0.179	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
D/Q	0.4501	ambiguous	0.5705	pathogenic	-0.291	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
D/R	0.5718	likely_pathogenic	0.7018	pathogenic	0.341	Stabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
D/S	0.1781	likely_benign	0.2353	benign	-0.547	Destabilizing	0.997	D	0.577	neutral	None	None	None	None	N
D/T	0.2927	likely_benign	0.3868	ambiguous	-0.321	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
D/V	0.2327	likely_benign	0.3095	benign	0.179	Stabilizing	0.999	D	0.7	prob.neutral	N	0.437449602	None	None	N
D/W	0.8802	likely_pathogenic	0.9266	pathogenic	0.323	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
D/Y	0.2106	likely_benign	0.2804	benign	0.366	Stabilizing	1.0	D	0.718	prob.delet.	N	0.350531108	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.