TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31644	95155;95156;95157	chr2:178546401;178546400;178546399	chr2:179411128;179411127;179411126
N2AB	30003	90232;90233;90234	chr2:178546401;178546400;178546399	chr2:179411128;179411127;179411126
N2A	29076	87451;87452;87453	chr2:178546401;178546400;178546399	chr2:179411128;179411127;179411126
N2B	22579	67960;67961;67962	chr2:178546401;178546400;178546399	chr2:179411128;179411127;179411126
Novex-1	22704	68335;68336;68337	chr2:178546401;178546400;178546399	chr2:179411128;179411127;179411126
Novex-2	22771	68536;68537;68538	chr2:178546401;178546400;178546399	chr2:179411128;179411127;179411126
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-152
• Domain position: 24
• Structural Position: 43
• Q(SASA): 0.5718
• 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
E/D	rs1281349835	-0.378	0.999	N	0.541	0.185	0.46017455471	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/D	rs1281349835	-0.378	0.999	N	0.541	0.185	0.46017455471	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1281349835	-0.378	0.999	N	0.541	0.185	0.46017455471	gnomAD-4.0.0	1.85912E-05	None	None	None	None	I	None	1.33483E-05	0	None	0	0	None	0	0	2.45813E-05	0	0
E/K	rs958594083	0.168	0.999	N	0.699	0.43	0.457286136841	gnomAD-2.1.1	1.79E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.91E-05	0
E/K	rs958594083	0.168	0.999	N	0.699	0.43	0.457286136841	gnomAD-3.1.2	3.95E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	7.35E-05	0	0
E/K	rs958594083	0.168	0.999	N	0.699	0.43	0.457286136841	gnomAD-4.0.0	2.04513E-05	None	None	None	None	I	None	1.33518E-05	0	None	0	0	None	0	0	2.71243E-05	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
E/A	0.1537	likely_benign	0.1467	benign	-0.235	Destabilizing	0.999	D	0.703	prob.neutral	N	0.457196349	None	None	I
E/C	0.8853	likely_pathogenic	0.8769	pathogenic	-0.007	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
E/D	0.1545	likely_benign	0.1538	benign	-0.289	Destabilizing	0.999	D	0.541	neutral	N	0.518012734	None	None	I
E/F	0.7868	likely_pathogenic	0.7785	pathogenic	-0.168	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
E/G	0.3101	likely_benign	0.3089	benign	-0.41	Destabilizing	1.0	D	0.675	prob.neutral	N	0.512207737	None	None	I
E/H	0.6284	likely_pathogenic	0.6238	pathogenic	0.146	Stabilizing	1.0	D	0.615	neutral	None	None	None	None	I
E/I	0.3438	ambiguous	0.3319	benign	0.183	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
E/K	0.2501	likely_benign	0.2503	benign	0.423	Stabilizing	0.999	D	0.699	prob.neutral	N	0.464679681	None	None	I
E/L	0.355	ambiguous	0.3576	ambiguous	0.183	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
E/M	0.4628	ambiguous	0.4506	ambiguous	0.185	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	I
E/N	0.3743	ambiguous	0.3574	ambiguous	0.138	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
E/P	0.4539	ambiguous	0.4413	ambiguous	0.063	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	I
E/Q	0.1781	likely_benign	0.1749	benign	0.164	Stabilizing	1.0	D	0.622	neutral	N	0.496560026	None	None	I
E/R	0.3941	ambiguous	0.3896	ambiguous	0.612	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
E/S	0.2668	likely_benign	0.2538	benign	-0.013	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	I
E/T	0.2916	likely_benign	0.2752	benign	0.132	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
E/V	0.1988	likely_benign	0.1961	benign	0.063	Stabilizing	1.0	D	0.695	prob.neutral	N	0.506913093	None	None	I
E/W	0.9381	likely_pathogenic	0.9348	pathogenic	-0.051	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
E/Y	0.6781	likely_pathogenic	0.6698	pathogenic	0.074	Stabilizing	1.0	D	0.647	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.