TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32325	97198;97199;97200	chr2:178542881;178542880;178542879	chr2:179407608;179407607;179407606
N2AB	30684	92275;92276;92277	chr2:178542881;178542880;178542879	chr2:179407608;179407607;179407606
N2A	29757	89494;89495;89496	chr2:178542881;178542880;178542879	chr2:179407608;179407607;179407606
N2B	23260	70003;70004;70005	chr2:178542881;178542880;178542879	chr2:179407608;179407607;179407606
Novex-1	23385	70378;70379;70380	chr2:178542881;178542880;178542879	chr2:179407608;179407607;179407606
Novex-2	23452	70579;70580;70581	chr2:178542881;178542880;178542879	chr2:179407608;179407607;179407606
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-154
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.5163
• 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
E/Q	rs1196060333	-0.087	0.994	N	0.598	0.208	0.19670166235	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
E/Q	rs1196060333	-0.087	0.994	N	0.598	0.208	0.19670166235	gnomAD-4.0.0	2.7371E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59831E-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
E/A	0.2251	likely_benign	0.2069	benign	-0.596	Destabilizing	0.961	D	0.594	neutral	N	0.488974253	None	None	N
E/C	0.8658	likely_pathogenic	0.8569	pathogenic	-0.363	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/D	0.1981	likely_benign	0.1836	benign	-0.797	Destabilizing	0.031	N	0.248	neutral	N	0.508349448	None	None	N
E/F	0.8125	likely_pathogenic	0.7857	pathogenic	-0.006	Destabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	N
E/G	0.3689	ambiguous	0.3406	ambiguous	-0.922	Destabilizing	0.98	D	0.601	neutral	N	0.459161608	None	None	N
E/H	0.5035	ambiguous	0.4575	ambiguous	-0.033	Destabilizing	1.0	D	0.6	neutral	None	None	None	None	N
E/I	0.3852	ambiguous	0.3606	ambiguous	0.279	Stabilizing	0.983	D	0.651	neutral	None	None	None	None	N
E/K	0.2957	likely_benign	0.2657	benign	-0.232	Destabilizing	0.98	D	0.588	neutral	N	0.45093594	None	None	N
E/L	0.4886	ambiguous	0.4484	ambiguous	0.279	Stabilizing	0.942	D	0.617	neutral	None	None	None	None	N
E/M	0.5096	ambiguous	0.4742	ambiguous	0.459	Stabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/N	0.3331	likely_benign	0.3112	benign	-0.769	Destabilizing	0.991	D	0.587	neutral	None	None	None	None	N
E/P	0.8813	likely_pathogenic	0.8702	pathogenic	0.009	Stabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
E/Q	0.1575	likely_benign	0.1489	benign	-0.643	Destabilizing	0.994	D	0.598	neutral	N	0.476045028	None	None	N
E/R	0.4134	ambiguous	0.3828	ambiguous	0.121	Stabilizing	0.996	D	0.613	neutral	None	None	None	None	N
E/S	0.2333	likely_benign	0.2116	benign	-0.996	Destabilizing	0.97	D	0.562	neutral	None	None	None	None	N
E/T	0.2017	likely_benign	0.1984	benign	-0.724	Destabilizing	0.97	D	0.599	neutral	None	None	None	None	N
E/V	0.2258	likely_benign	0.2109	benign	0.009	Stabilizing	0.433	N	0.452	neutral	N	0.44989579	None	None	N
E/W	0.9496	likely_pathogenic	0.934	pathogenic	0.258	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/Y	0.7521	likely_pathogenic	0.7004	pathogenic	0.254	Stabilizing	0.999	D	0.695	prob.neutral	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.