TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25128	75607;75608;75609	chr2:178570750;178570749;178570748	chr2:179435477;179435476;179435475
N2AB	23487	70684;70685;70686	chr2:178570750;178570749;178570748	chr2:179435477;179435476;179435475
N2A	22560	67903;67904;67905	chr2:178570750;178570749;178570748	chr2:179435477;179435476;179435475
N2B	16063	48412;48413;48414	chr2:178570750;178570749;178570748	chr2:179435477;179435476;179435475
Novex-1	16188	48787;48788;48789	chr2:178570750;178570749;178570748	chr2:179435477;179435476;179435475
Novex-2	16255	48988;48989;48990	chr2:178570750;178570749;178570748	chr2:179435477;179435476;179435475
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-134
• Domain position: 18
• Structural Position: 26
• Q(SASA): 0.4411
• 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
S/T	None	None	None	N	0.121	0.099	0.0297737177859	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0781	likely_benign	0.0731	benign	-0.719	Destabilizing	None	N	0.129	neutral	N	0.463771951	None	None	N
S/C	0.0918	likely_benign	0.0896	benign	-0.411	Destabilizing	0.356	N	0.393	neutral	None	None	None	None	N
S/D	0.3714	ambiguous	0.3627	ambiguous	0.133	Stabilizing	0.072	N	0.181	neutral	None	None	None	None	N
S/E	0.516	ambiguous	0.4874	ambiguous	0.104	Stabilizing	0.072	N	0.177	neutral	None	None	None	None	N
S/F	0.2015	likely_benign	0.1861	benign	-1.037	Destabilizing	None	N	0.228	neutral	None	None	None	None	N
S/G	0.0931	likely_benign	0.0924	benign	-0.93	Destabilizing	0.016	N	0.191	neutral	None	None	None	None	N
S/H	0.3288	likely_benign	0.3036	benign	-1.345	Destabilizing	0.628	D	0.393	neutral	None	None	None	None	N
S/I	0.1286	likely_benign	0.1158	benign	-0.273	Destabilizing	0.001	N	0.225	neutral	None	None	None	None	N
S/K	0.6163	likely_pathogenic	0.5859	pathogenic	-0.599	Destabilizing	0.072	N	0.175	neutral	None	None	None	None	N
S/L	0.0908	likely_benign	0.0826	benign	-0.273	Destabilizing	None	N	0.157	neutral	N	0.457897841	None	None	N
S/M	0.159	likely_benign	0.1445	benign	-0.017	Destabilizing	0.002	N	0.227	neutral	None	None	None	None	N
S/N	0.1099	likely_benign	0.1086	benign	-0.453	Destabilizing	0.072	N	0.271	neutral	None	None	None	None	N
S/P	0.1294	likely_benign	0.1413	benign	-0.389	Destabilizing	0.295	N	0.453	neutral	N	0.447647706	None	None	N
S/Q	0.4634	ambiguous	0.4278	ambiguous	-0.604	Destabilizing	0.356	N	0.338	neutral	None	None	None	None	N
S/R	0.5766	likely_pathogenic	0.5429	ambiguous	-0.457	Destabilizing	0.072	N	0.457	neutral	None	None	None	None	N
S/T	0.0683	likely_benign	0.0681	benign	-0.537	Destabilizing	None	N	0.121	neutral	N	0.361143442	None	None	N
S/V	0.1331	likely_benign	0.1184	benign	-0.389	Destabilizing	0.016	N	0.333	neutral	None	None	None	None	N
S/W	0.3356	likely_benign	0.3092	benign	-1.0	Destabilizing	0.676	D	0.375	neutral	None	None	None	None	N
S/Y	0.1753	likely_benign	0.1633	benign	-0.744	Destabilizing	0.12	N	0.445	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.