TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15143	45652;45653;45654	chr2:178621291;178621290;178621289	chr2:179486018;179486017;179486016
N2AB	13502	40729;40730;40731	chr2:178621291;178621290;178621289	chr2:179486018;179486017;179486016
N2A	12575	37948;37949;37950	chr2:178621291;178621290;178621289	chr2:179486018;179486017;179486016
N2B	6078	18457;18458;18459	chr2:178621291;178621290;178621289	chr2:179486018;179486017;179486016
Novex-1	6203	18832;18833;18834	chr2:178621291;178621290;178621289	chr2:179486018;179486017;179486016
Novex-2	6270	19033;19034;19035	chr2:178621291;178621290;178621289	chr2:179486018;179486017;179486016
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-103
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0934
• 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/V	rs778468554	-1.316	0.001	N	0.24	0.113	0.249502417897	gnomAD-2.1.1	8.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.96E-06	0
I/V	rs778468554	-1.316	0.001	N	0.24	0.113	0.249502417897	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs778468554	-1.316	0.001	N	0.24	0.113	0.249502417897	gnomAD-4.0.0	3.7219E-06	None	None	None	None	N	None	1.33668E-05	0	None	0	2.24417E-05	None	0	0	2.54427E-06	1.09871E-05	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	0.8754	likely_pathogenic	0.8545	pathogenic	-2.869	Highly Destabilizing	0.25	N	0.641	neutral	None	None	None	None	N
I/C	0.9552	likely_pathogenic	0.932	pathogenic	-2.143	Highly Destabilizing	0.992	D	0.753	deleterious	None	None	None	None	N
I/D	0.997	likely_pathogenic	0.9956	pathogenic	-3.313	Highly Destabilizing	0.972	D	0.812	deleterious	None	None	None	None	N
I/E	0.9924	likely_pathogenic	0.9901	pathogenic	-3.074	Highly Destabilizing	0.92	D	0.798	deleterious	None	None	None	None	N
I/F	0.6254	likely_pathogenic	0.541	ambiguous	-1.685	Destabilizing	0.739	D	0.739	prob.delet.	None	None	None	None	N
I/G	0.987	likely_pathogenic	0.9834	pathogenic	-3.389	Highly Destabilizing	0.92	D	0.795	deleterious	None	None	None	None	N
I/H	0.9897	likely_pathogenic	0.986	pathogenic	-2.783	Highly Destabilizing	0.992	D	0.789	deleterious	None	None	None	None	N
I/K	0.9879	likely_pathogenic	0.9857	pathogenic	-2.091	Highly Destabilizing	0.896	D	0.797	deleterious	D	0.556965219	None	None	N
I/L	0.2663	likely_benign	0.2367	benign	-1.34	Destabilizing	0.002	N	0.267	neutral	N	0.45170929	None	None	N
I/M	0.3095	likely_benign	0.2883	benign	-1.448	Destabilizing	0.81	D	0.685	prob.neutral	N	0.519940245	None	None	N
I/N	0.9583	likely_pathogenic	0.9448	pathogenic	-2.513	Highly Destabilizing	0.972	D	0.82	deleterious	None	None	None	None	N
I/P	0.9908	likely_pathogenic	0.9882	pathogenic	-1.836	Destabilizing	0.972	D	0.815	deleterious	None	None	None	None	N
I/Q	0.9862	likely_pathogenic	0.9824	pathogenic	-2.351	Highly Destabilizing	0.972	D	0.818	deleterious	None	None	None	None	N
I/R	0.9804	likely_pathogenic	0.9762	pathogenic	-1.815	Destabilizing	0.896	D	0.82	deleterious	D	0.556965219	None	None	N
I/S	0.9181	likely_pathogenic	0.9032	pathogenic	-3.147	Highly Destabilizing	0.92	D	0.771	deleterious	None	None	None	None	N
I/T	0.7735	likely_pathogenic	0.7589	pathogenic	-2.775	Highly Destabilizing	0.549	D	0.701	prob.neutral	N	0.491330852	None	None	N
I/V	0.0821	likely_benign	0.0869	benign	-1.836	Destabilizing	0.001	N	0.24	neutral	N	0.306386506	None	None	N
I/W	0.994	likely_pathogenic	0.9912	pathogenic	-2.056	Highly Destabilizing	0.992	D	0.797	deleterious	None	None	None	None	N
I/Y	0.9666	likely_pathogenic	0.9513	pathogenic	-1.86	Destabilizing	0.92	D	0.786	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.