TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5197	15814;15815;15816	chr2:178733800;178733799;178733798	chr2:179598527;179598526;179598525
N2AB	4880	14863;14864;14865	chr2:178733800;178733799;178733798	chr2:179598527;179598526;179598525
N2A	3953	12082;12083;12084	chr2:178733800;178733799;178733798	chr2:179598527;179598526;179598525
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-35
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1456
• 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
I/L	rs781467868	-0.794	0.02	N	0.23	0.116	0.3571064206	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	1.73853E-04	None	0	0	None	0	None	0	0	0
I/L	rs781467868	-0.794	0.02	N	0.23	0.116	0.3571064206	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96541E-04	0	0	0	None	0	0	0	0	0
I/L	rs781467868	-0.794	0.02	N	0.23	0.116	0.3571064206	gnomAD-4.0.0	1.15295E-05	None	None	None	None	N	None	0	1.52542E-04	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
I/A	0.772	likely_pathogenic	0.8127	pathogenic	-2.042	Highly Destabilizing	0.953	D	0.513	neutral	None	None	None	None	N
I/C	0.9224	likely_pathogenic	0.9431	pathogenic	-1.39	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
I/D	0.9909	likely_pathogenic	0.9928	pathogenic	-1.35	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
I/E	0.9803	likely_pathogenic	0.9847	pathogenic	-1.264	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
I/F	0.4722	ambiguous	0.5132	ambiguous	-1.297	Destabilizing	0.982	D	0.615	neutral	D	0.634655212	None	None	N
I/G	0.9654	likely_pathogenic	0.9752	pathogenic	-2.463	Highly Destabilizing	0.998	D	0.75	deleterious	None	None	None	None	N
I/H	0.9642	likely_pathogenic	0.9727	pathogenic	-1.716	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
I/K	0.9399	likely_pathogenic	0.9498	pathogenic	-1.359	Destabilizing	0.993	D	0.754	deleterious	None	None	None	None	N
I/L	0.1539	likely_benign	0.1514	benign	-0.91	Destabilizing	0.02	N	0.23	neutral	N	0.50307912	None	None	N
I/M	0.2443	likely_benign	0.2718	benign	-0.831	Destabilizing	0.982	D	0.607	neutral	N	0.502687105	None	None	N
I/N	0.9004	likely_pathogenic	0.9235	pathogenic	-1.272	Destabilizing	0.997	D	0.759	deleterious	D	0.712824913	None	None	N
I/P	0.913	likely_pathogenic	0.9263	pathogenic	-1.259	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
I/Q	0.9486	likely_pathogenic	0.9611	pathogenic	-1.336	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
I/R	0.9085	likely_pathogenic	0.923	pathogenic	-0.923	Destabilizing	0.993	D	0.76	deleterious	None	None	None	None	N
I/S	0.8769	likely_pathogenic	0.9056	pathogenic	-2.023	Highly Destabilizing	0.991	D	0.657	neutral	D	0.564733331	None	None	N
I/T	0.8223	likely_pathogenic	0.8612	pathogenic	-1.802	Destabilizing	0.991	D	0.637	neutral	D	0.574139497	None	None	N
I/V	0.0889	likely_benign	0.0948	benign	-1.259	Destabilizing	0.58	D	0.417	neutral	D	0.553363523	None	None	N
I/W	0.9762	likely_pathogenic	0.9799	pathogenic	-1.422	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
I/Y	0.9053	likely_pathogenic	0.921	pathogenic	-1.185	Destabilizing	0.993	D	0.693	prob.neutral	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.