TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34384	103375;103376;103377	chr2:178533465;178533464;178533463	chr2:179398192;179398191;179398190
N2AB	32743	98452;98453;98454	chr2:178533465;178533464;178533463	chr2:179398192;179398191;179398190
N2A	31816	95671;95672;95673	chr2:178533465;178533464;178533463	chr2:179398192;179398191;179398190
N2B	25319	76180;76181;76182	chr2:178533465;178533464;178533463	chr2:179398192;179398191;179398190
Novex-1	25444	76555;76556;76557	chr2:178533465;178533464;178533463	chr2:179398192;179398191;179398190
Novex-2	25511	76756;76757;76758	chr2:178533465;178533464;178533463	chr2:179398192;179398191;179398190
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-162
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0438
• 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
I/N	rs1435527858	-2.67	0.996	N	0.842	0.641	0.852766357386	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/N	rs1435527858	-2.67	0.996	N	0.842	0.641	0.852766357386	gnomAD-4.0.0	1.59184E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85984E-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
I/A	0.9714	likely_pathogenic	0.9562	pathogenic	-2.671	Highly Destabilizing	0.863	D	0.658	neutral	None	None	None	None	N
I/C	0.9742	likely_pathogenic	0.9676	pathogenic	-1.55	Destabilizing	0.1	N	0.573	neutral	None	None	None	None	N
I/D	0.9991	likely_pathogenic	0.999	pathogenic	-3.206	Highly Destabilizing	0.997	D	0.829	deleterious	None	None	None	None	N
I/E	0.9973	likely_pathogenic	0.9969	pathogenic	-2.899	Highly Destabilizing	0.997	D	0.817	deleterious	None	None	None	None	N
I/F	0.9001	likely_pathogenic	0.8668	pathogenic	-1.599	Destabilizing	0.92	D	0.699	prob.neutral	N	0.494256014	None	None	N
I/G	0.9935	likely_pathogenic	0.9917	pathogenic	-3.221	Highly Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	N
I/H	0.9989	likely_pathogenic	0.9985	pathogenic	-2.92	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
I/K	0.9973	likely_pathogenic	0.9966	pathogenic	-1.954	Destabilizing	0.991	D	0.811	deleterious	None	None	None	None	N
I/L	0.5596	ambiguous	0.4305	ambiguous	-0.989	Destabilizing	0.005	N	0.257	neutral	N	0.437189223	None	None	N
I/M	0.4867	ambiguous	0.3744	ambiguous	-1.18	Destabilizing	0.509	D	0.454	neutral	N	0.475400894	None	None	N
I/N	0.988	likely_pathogenic	0.9837	pathogenic	-2.705	Highly Destabilizing	0.996	D	0.842	deleterious	N	0.494429372	None	None	N
I/P	0.9986	likely_pathogenic	0.9983	pathogenic	-1.547	Destabilizing	0.997	D	0.839	deleterious	None	None	None	None	N
I/Q	0.997	likely_pathogenic	0.9961	pathogenic	-2.315	Highly Destabilizing	0.991	D	0.843	deleterious	None	None	None	None	N
I/R	0.9971	likely_pathogenic	0.9962	pathogenic	-2.155	Highly Destabilizing	0.991	D	0.827	deleterious	None	None	None	None	N
I/S	0.9854	likely_pathogenic	0.9785	pathogenic	-3.101	Highly Destabilizing	0.959	D	0.757	deleterious	N	0.441731038	None	None	N
I/T	0.9755	likely_pathogenic	0.9594	pathogenic	-2.641	Highly Destabilizing	0.959	D	0.719	prob.delet.	N	0.43465035	None	None	N
I/V	0.3157	likely_benign	0.238	benign	-1.547	Destabilizing	0.509	D	0.426	neutral	N	0.340198606	None	None	N
I/W	0.998	likely_pathogenic	0.9978	pathogenic	-1.838	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
I/Y	0.9895	likely_pathogenic	0.9883	pathogenic	-1.766	Destabilizing	0.997	D	0.774	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.