TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26416	79471;79472;79473	chr2:178566886;178566885;178566884	chr2:179431613;179431612;179431611
N2AB	24775	74548;74549;74550	chr2:178566886;178566885;178566884	chr2:179431613;179431612;179431611
N2A	23848	71767;71768;71769	chr2:178566886;178566885;178566884	chr2:179431613;179431612;179431611
N2B	17351	52276;52277;52278	chr2:178566886;178566885;178566884	chr2:179431613;179431612;179431611
Novex-1	17476	52651;52652;52653	chr2:178566886;178566885;178566884	chr2:179431613;179431612;179431611
Novex-2	17543	52852;52853;52854	chr2:178566886;178566885;178566884	chr2:179431613;179431612;179431611
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: Fn3-80
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3013
• 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/R	None	None	0.89	N	0.599	0.423	0.299770980665	gnomAD-4.0.0	1.59176E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02554E-05

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	0.1632	likely_benign	0.1827	benign	-0.49	Destabilizing	0.559	D	0.655	neutral	None	None	None	None	I
S/C	0.1352	likely_benign	0.1633	benign	-0.255	Destabilizing	0.997	D	0.61	neutral	N	0.492123293	None	None	I
S/D	0.9024	likely_pathogenic	0.9117	pathogenic	-0.249	Destabilizing	0.754	D	0.637	neutral	None	None	None	None	I
S/E	0.9391	likely_pathogenic	0.9399	pathogenic	-0.321	Destabilizing	0.754	D	0.639	neutral	None	None	None	None	I
S/F	0.7784	likely_pathogenic	0.8126	pathogenic	-0.95	Destabilizing	0.993	D	0.665	neutral	None	None	None	None	I
S/G	0.2584	likely_benign	0.2874	benign	-0.653	Destabilizing	0.822	D	0.621	neutral	N	0.46785593	None	None	I
S/H	0.768	likely_pathogenic	0.7795	pathogenic	-1.226	Destabilizing	0.978	D	0.588	neutral	None	None	None	None	I
S/I	0.7616	likely_pathogenic	0.7692	pathogenic	-0.181	Destabilizing	0.97	D	0.669	neutral	N	0.513074704	None	None	I
S/K	0.9717	likely_pathogenic	0.9722	pathogenic	-0.63	Destabilizing	0.019	N	0.435	neutral	None	None	None	None	I
S/L	0.3807	ambiguous	0.4308	ambiguous	-0.181	Destabilizing	0.86	D	0.662	neutral	None	None	None	None	I
S/M	0.5269	ambiguous	0.5341	ambiguous	0.254	Stabilizing	0.998	D	0.591	neutral	None	None	None	None	I
S/N	0.2942	likely_benign	0.2988	benign	-0.388	Destabilizing	0.058	N	0.453	neutral	N	0.484766233	None	None	I
S/P	0.9921	likely_pathogenic	0.9913	pathogenic	-0.253	Destabilizing	0.978	D	0.609	neutral	None	None	None	None	I
S/Q	0.86	likely_pathogenic	0.8661	pathogenic	-0.68	Destabilizing	0.956	D	0.65	neutral	None	None	None	None	I
S/R	0.945	likely_pathogenic	0.9472	pathogenic	-0.397	Destabilizing	0.89	D	0.599	neutral	N	0.49162586	None	None	I
S/T	0.279	likely_benign	0.2572	benign	-0.455	Destabilizing	0.822	D	0.659	neutral	N	0.489450267	None	None	I
S/V	0.6377	likely_pathogenic	0.6377	pathogenic	-0.253	Destabilizing	0.956	D	0.649	neutral	None	None	None	None	I
S/W	0.8632	likely_pathogenic	0.8728	pathogenic	-0.928	Destabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	I
S/Y	0.716	likely_pathogenic	0.7401	pathogenic	-0.665	Destabilizing	0.993	D	0.665	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.