TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20496	61711;61712;61713	chr2:178590239;178590238;178590237	chr2:179454966;179454965;179454964
N2AB	18855	56788;56789;56790	chr2:178590239;178590238;178590237	chr2:179454966;179454965;179454964
N2A	17928	54007;54008;54009	chr2:178590239;178590238;178590237	chr2:179454966;179454965;179454964
N2B	11431	34516;34517;34518	chr2:178590239;178590238;178590237	chr2:179454966;179454965;179454964
Novex-1	11556	34891;34892;34893	chr2:178590239;178590238;178590237	chr2:179454966;179454965;179454964
Novex-2	11623	35092;35093;35094	chr2:178590239;178590238;178590237	chr2:179454966;179454965;179454964
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-121
• Domain position: 18
• Structural Position: 30
• Q(SASA): 0.1323
• 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/F	None	None	0.989	N	0.692	0.305	0.554801812059	gnomAD-4.0.0	1.65244E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.54059E-05	0
I/M	rs886042497	None	0.989	N	0.657	0.288	0.606648057779	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/M	rs886042497	None	0.989	N	0.657	0.288	0.606648057779	gnomAD-4.0.0	7.54018E-06	None	None	None	None	N	None	0	3.45686E-05	None	0	0	None	0	0	8.55445E-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	0.9801	likely_pathogenic	0.9867	pathogenic	-2.411	Highly Destabilizing	0.97	D	0.7	prob.neutral	None	None	None	None	N
I/C	0.9685	likely_pathogenic	0.9771	pathogenic	-1.599	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
I/D	0.9993	likely_pathogenic	0.9995	pathogenic	-3.066	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
I/E	0.9983	likely_pathogenic	0.9988	pathogenic	-2.786	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
I/F	0.5668	likely_pathogenic	0.6296	pathogenic	-1.523	Destabilizing	0.989	D	0.692	prob.neutral	N	0.43559642	None	None	N
I/G	0.9957	likely_pathogenic	0.9971	pathogenic	-2.949	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
I/H	0.9956	likely_pathogenic	0.9964	pathogenic	-2.43	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
I/K	0.996	likely_pathogenic	0.9966	pathogenic	-1.887	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
I/L	0.1685	likely_benign	0.1826	benign	-0.814	Destabilizing	0.031	N	0.275	neutral	N	0.363541534	None	None	N
I/M	0.325	likely_benign	0.3621	ambiguous	-0.803	Destabilizing	0.989	D	0.657	neutral	N	0.485150954	None	None	N
I/N	0.9912	likely_pathogenic	0.9925	pathogenic	-2.473	Highly Destabilizing	0.998	D	0.853	deleterious	N	0.499330494	None	None	N
I/P	0.9977	likely_pathogenic	0.998	pathogenic	-1.335	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
I/Q	0.9957	likely_pathogenic	0.9964	pathogenic	-2.229	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
I/R	0.9941	likely_pathogenic	0.995	pathogenic	-1.847	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
I/S	0.9913	likely_pathogenic	0.9935	pathogenic	-3.049	Highly Destabilizing	0.994	D	0.812	deleterious	N	0.5106868	None	None	N
I/T	0.9906	likely_pathogenic	0.9935	pathogenic	-2.612	Highly Destabilizing	0.961	D	0.739	prob.delet.	N	0.51043331	None	None	N
I/V	0.2084	likely_benign	0.2617	benign	-1.335	Destabilizing	0.248	N	0.237	neutral	N	0.472760447	None	None	N
I/W	0.9924	likely_pathogenic	0.9942	pathogenic	-1.864	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
I/Y	0.9586	likely_pathogenic	0.966	pathogenic	-1.57	Destabilizing	0.999	D	0.747	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.