TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15165	45718;45719;45720	chr2:178621225;178621224;178621223	chr2:179485952;179485951;179485950
N2AB	13524	40795;40796;40797	chr2:178621225;178621224;178621223	chr2:179485952;179485951;179485950
N2A	12597	38014;38015;38016	chr2:178621225;178621224;178621223	chr2:179485952;179485951;179485950
N2B	6100	18523;18524;18525	chr2:178621225;178621224;178621223	chr2:179485952;179485951;179485950
Novex-1	6225	18898;18899;18900	chr2:178621225;178621224;178621223	chr2:179485952;179485951;179485950
Novex-2	6292	19099;19100;19101	chr2:178621225;178621224;178621223	chr2:179485952;179485951;179485950
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-103
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.1607
• 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
Y/C	None	None	1.0	D	0.8	0.535	0.630178222335	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
Y/A	0.9299	likely_pathogenic	0.9059	pathogenic	-3.025	Highly Destabilizing	0.996	D	0.646	neutral	None	None	None	None	N
Y/C	0.4757	ambiguous	0.4594	ambiguous	-1.932	Destabilizing	1.0	D	0.8	deleterious	D	0.706220021	None	None	N
Y/D	0.9443	likely_pathogenic	0.9212	pathogenic	-2.747	Highly Destabilizing	0.998	D	0.813	deleterious	D	0.743986195	None	None	N
Y/E	0.9691	likely_pathogenic	0.9595	pathogenic	-2.585	Highly Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
Y/F	0.1704	likely_benign	0.1618	benign	-1.207	Destabilizing	0.994	D	0.495	neutral	N	0.505562642	None	None	N
Y/G	0.9166	likely_pathogenic	0.8962	pathogenic	-3.43	Highly Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
Y/H	0.6329	likely_pathogenic	0.561	ambiguous	-1.893	Destabilizing	0.391	N	0.343	neutral	D	0.580528872	None	None	N
Y/I	0.7334	likely_pathogenic	0.7152	pathogenic	-1.714	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/K	0.9642	likely_pathogenic	0.9556	pathogenic	-2.091	Highly Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
Y/L	0.7495	likely_pathogenic	0.7395	pathogenic	-1.714	Destabilizing	0.996	D	0.606	neutral	None	None	None	None	N
Y/M	0.8613	likely_pathogenic	0.8383	pathogenic	-1.472	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
Y/N	0.7218	likely_pathogenic	0.6756	pathogenic	-2.701	Highly Destabilizing	0.997	D	0.775	deleterious	D	0.706309319	None	None	N
Y/P	0.9935	likely_pathogenic	0.9904	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/Q	0.9502	likely_pathogenic	0.936	pathogenic	-2.528	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
Y/R	0.9128	likely_pathogenic	0.8941	pathogenic	-1.69	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
Y/S	0.8553	likely_pathogenic	0.8179	pathogenic	-3.172	Highly Destabilizing	0.998	D	0.733	prob.delet.	D	0.666530952	None	None	N
Y/T	0.8711	likely_pathogenic	0.8301	pathogenic	-2.893	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
Y/V	0.6452	likely_pathogenic	0.6188	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
Y/W	0.6171	likely_pathogenic	0.5735	pathogenic	-0.622	Destabilizing	1.0	D	0.723	prob.delet.	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.