TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26070	78433;78434;78435	chr2:178567924;178567923;178567922	chr2:179432651;179432650;179432649
N2AB	24429	73510;73511;73512	chr2:178567924;178567923;178567922	chr2:179432651;179432650;179432649
N2A	23502	70729;70730;70731	chr2:178567924;178567923;178567922	chr2:179432651;179432650;179432649
N2B	17005	51238;51239;51240	chr2:178567924;178567923;178567922	chr2:179432651;179432650;179432649
Novex-1	17130	51613;51614;51615	chr2:178567924;178567923;178567922	chr2:179432651;179432650;179432649
Novex-2	17197	51814;51815;51816	chr2:178567924;178567923;178567922	chr2:179432651;179432650;179432649
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: Fn3-77
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.8127
• Predicted PPI site: I

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/T	None	None	1.0	N	0.539	0.439	0.740325958804	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
I/V	rs765860384	-0.108	0.993	N	0.342	0.165	0.512079609283	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/V	rs765860384	-0.108	0.993	N	0.342	0.165	0.512079609283	gnomAD-4.0.0	1.59172E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85948E-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	0.3223	likely_benign	0.3596	ambiguous	-0.539	Destabilizing	0.999	D	0.494	neutral	None	None	None	None	I
I/C	0.8297	likely_pathogenic	0.8471	pathogenic	-0.795	Destabilizing	1.0	D	0.581	neutral	None	None	None	None	I
I/D	0.8977	likely_pathogenic	0.9196	pathogenic	-0.123	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
I/E	0.8015	likely_pathogenic	0.844	pathogenic	-0.213	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
I/F	0.3463	ambiguous	0.3574	ambiguous	-0.581	Destabilizing	1.0	D	0.581	neutral	N	0.485750057	None	None	I
I/G	0.8388	likely_pathogenic	0.8567	pathogenic	-0.672	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	I
I/H	0.7677	likely_pathogenic	0.7976	pathogenic	0.044	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	I
I/K	0.5751	likely_pathogenic	0.612	pathogenic	-0.347	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	I
I/L	0.1479	likely_benign	0.1507	benign	-0.315	Destabilizing	0.993	D	0.312	neutral	N	0.4662819	None	None	I
I/M	0.1193	likely_benign	0.122	benign	-0.494	Destabilizing	1.0	D	0.567	neutral	N	0.469418205	None	None	I
I/N	0.6034	likely_pathogenic	0.626	pathogenic	-0.245	Destabilizing	1.0	D	0.645	neutral	N	0.513552985	None	None	I
I/P	0.8466	likely_pathogenic	0.8482	pathogenic	-0.358	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	I
I/Q	0.6751	likely_pathogenic	0.7084	pathogenic	-0.435	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
I/R	0.4526	ambiguous	0.4906	ambiguous	0.171	Stabilizing	1.0	D	0.647	neutral	None	None	None	None	I
I/S	0.4724	ambiguous	0.4947	ambiguous	-0.678	Destabilizing	1.0	D	0.58	neutral	N	0.44684799	None	None	I
I/T	0.3374	likely_benign	0.3547	ambiguous	-0.66	Destabilizing	1.0	D	0.539	neutral	N	0.502085197	None	None	I
I/V	0.0938	likely_benign	0.0969	benign	-0.358	Destabilizing	0.993	D	0.342	neutral	N	0.495313941	None	None	I
I/W	0.912	likely_pathogenic	0.9259	pathogenic	-0.594	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
I/Y	0.7495	likely_pathogenic	0.7767	pathogenic	-0.356	Destabilizing	1.0	D	0.58	neutral	None	None	None	None	I

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.