TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21544	64855;64856;64857	chr2:178585114;178585113;178585112	chr2:179449841;179449840;179449839
N2AB	19903	59932;59933;59934	chr2:178585114;178585113;178585112	chr2:179449841;179449840;179449839
N2A	18976	57151;57152;57153	chr2:178585114;178585113;178585112	chr2:179449841;179449840;179449839
N2B	12479	37660;37661;37662	chr2:178585114;178585113;178585112	chr2:179449841;179449840;179449839
Novex-1	12604	38035;38036;38037	chr2:178585114;178585113;178585112	chr2:179449841;179449840;179449839
Novex-2	12671	38236;38237;38238	chr2:178585114;178585113;178585112	chr2:179449841;179449840;179449839
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-124
• Domain position: 76
• Structural Position: 162
• Q(SASA): 0.6988
• 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
S/N	rs1231941272	0.179	0.999	D	0.478	0.352	0.437207349437	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
S/N	rs1231941272	0.179	0.999	D	0.478	0.352	0.437207349437	gnomAD-4.0.0	1.5953E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86572E-06	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
S/A	0.0712	likely_benign	0.0735	benign	-0.262	Destabilizing	0.998	D	0.398	neutral	None	None	None	None	I
S/C	0.1305	likely_benign	0.1381	benign	-0.4	Destabilizing	1.0	D	0.607	neutral	N	0.509400261	None	None	I
S/D	0.4901	ambiguous	0.4557	ambiguous	-0.138	Destabilizing	0.999	D	0.499	neutral	None	None	None	None	I
S/E	0.5426	ambiguous	0.5222	ambiguous	-0.25	Destabilizing	0.999	D	0.484	neutral	None	None	None	None	I
S/F	0.256	likely_benign	0.2519	benign	-1.039	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
S/G	0.0987	likely_benign	0.1019	benign	-0.27	Destabilizing	0.999	D	0.345	neutral	N	0.521498543	None	None	I
S/H	0.3989	ambiguous	0.3736	ambiguous	-0.617	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	I
S/I	0.1037	likely_benign	0.1016	benign	-0.362	Destabilizing	1.0	D	0.64	neutral	N	0.514207211	None	None	I
S/K	0.6579	likely_pathogenic	0.6036	pathogenic	-0.407	Destabilizing	0.999	D	0.493	neutral	None	None	None	None	I
S/L	0.0895	likely_benign	0.0902	benign	-0.362	Destabilizing	1.0	D	0.539	neutral	None	None	None	None	I
S/M	0.1617	likely_benign	0.1606	benign	-0.224	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
S/N	0.1537	likely_benign	0.132	benign	-0.183	Destabilizing	0.999	D	0.478	neutral	D	0.53631328	None	None	I
S/P	0.2021	likely_benign	0.2068	benign	-0.309	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	I
S/Q	0.4814	ambiguous	0.4482	ambiguous	-0.409	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	I
S/R	0.603	likely_pathogenic	0.5708	pathogenic	-0.196	Destabilizing	1.0	D	0.579	neutral	N	0.520978468	None	None	I
S/T	0.0687	likely_benign	0.0708	benign	-0.3	Destabilizing	0.999	D	0.337	neutral	D	0.528597874	None	None	I
S/V	0.121	likely_benign	0.1224	benign	-0.309	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
S/W	0.513	ambiguous	0.5402	ambiguous	-1.122	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
S/Y	0.2766	likely_benign	0.2811	benign	-0.82	Destabilizing	1.0	D	0.679	prob.neutral	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.