TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21247	63964;63965;63966	chr2:178587570;178587569;178587568	chr2:179452297;179452296;179452295
N2AB	19606	59041;59042;59043	chr2:178587570;178587569;178587568	chr2:179452297;179452296;179452295
N2A	18679	56260;56261;56262	chr2:178587570;178587569;178587568	chr2:179452297;179452296;179452295
N2B	12182	36769;36770;36771	chr2:178587570;178587569;178587568	chr2:179452297;179452296;179452295
Novex-1	12307	37144;37145;37146	chr2:178587570;178587569;178587568	chr2:179452297;179452296;179452295
Novex-2	12374	37345;37346;37347	chr2:178587570;178587569;178587568	chr2:179452297;179452296;179452295
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-123
• Domain position: 71
• Structural Position: 157
• Q(SASA): 0.2175
• 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
T/A	None	None	0.489	N	0.621	0.297	0.374613414588	gnomAD-4.0.0	1.59453E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86226E-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
T/A	0.1461	likely_benign	0.161	benign	-1.068	Destabilizing	0.489	N	0.621	neutral	N	0.502026293	None	None	N
T/C	0.43	ambiguous	0.4791	ambiguous	-0.829	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
T/D	0.6884	likely_pathogenic	0.6952	pathogenic	-0.979	Destabilizing	0.86	D	0.699	prob.neutral	None	None	None	None	N
T/E	0.5555	ambiguous	0.5547	ambiguous	-0.857	Destabilizing	0.754	D	0.66	neutral	None	None	None	None	N
T/F	0.3482	ambiguous	0.3714	ambiguous	-0.8	Destabilizing	0.978	D	0.794	deleterious	None	None	None	None	N
T/G	0.394	ambiguous	0.453	ambiguous	-1.432	Destabilizing	0.754	D	0.703	prob.neutral	None	None	None	None	N
T/H	0.3038	likely_benign	0.326	benign	-1.629	Destabilizing	0.092	N	0.641	neutral	None	None	None	None	N
T/I	0.2402	likely_benign	0.2482	benign	-0.146	Destabilizing	0.97	D	0.751	deleterious	N	0.489860293	None	None	N
T/K	0.3827	ambiguous	0.3779	ambiguous	-0.723	Destabilizing	0.014	N	0.476	neutral	D	0.526149428	None	None	N
T/L	0.1293	likely_benign	0.1377	benign	-0.146	Destabilizing	0.86	D	0.673	neutral	None	None	None	None	N
T/M	0.1141	likely_benign	0.1227	benign	-0.073	Destabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	N
T/N	0.2019	likely_benign	0.2184	benign	-1.075	Destabilizing	0.86	D	0.645	neutral	None	None	None	None	N
T/P	0.696	likely_pathogenic	0.6971	pathogenic	-0.42	Destabilizing	0.97	D	0.74	deleterious	D	0.546832858	None	None	N
T/Q	0.3101	likely_benign	0.3365	benign	-1.032	Destabilizing	0.956	D	0.745	deleterious	None	None	None	None	N
T/R	0.3575	ambiguous	0.3381	benign	-0.755	Destabilizing	0.89	D	0.717	prob.delet.	N	0.483237248	None	None	N
T/S	0.1504	likely_benign	0.1746	benign	-1.334	Destabilizing	0.058	N	0.433	neutral	N	0.504495055	None	None	N
T/V	0.1902	likely_benign	0.2002	benign	-0.42	Destabilizing	0.86	D	0.634	neutral	None	None	None	None	N
T/W	0.723	likely_pathogenic	0.7605	pathogenic	-0.83	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
T/Y	0.3689	ambiguous	0.3923	ambiguous	-0.524	Destabilizing	0.956	D	0.799	deleterious	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.