TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20635	62128;62129;62130	chr2:178589822;178589821;178589820	chr2:179454549;179454548;179454547
N2AB	18994	57205;57206;57207	chr2:178589822;178589821;178589820	chr2:179454549;179454548;179454547
N2A	18067	54424;54425;54426	chr2:178589822;178589821;178589820	chr2:179454549;179454548;179454547
N2B	11570	34933;34934;34935	chr2:178589822;178589821;178589820	chr2:179454549;179454548;179454547
Novex-1	11695	35308;35309;35310	chr2:178589822;178589821;178589820	chr2:179454549;179454548;179454547
Novex-2	11762	35509;35510;35511	chr2:178589822;178589821;178589820	chr2:179454549;179454548;179454547
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-37
• Domain position: 67
• Structural Position: 100
• Q(SASA): 0.8034
• 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
N/D	rs2049831678	None	0.979	N	0.443	0.289	0.202949470691	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
N/K	rs749547976	0.466	0.979	N	0.454	0.246	0.144782658237	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
N/K	rs749547976	0.466	0.979	N	0.454	0.246	0.144782658237	gnomAD-4.0.0	1.59184E-06	None	None	None	None	I	None	0	0	None	0	2.77624E-05	None	0	0	0	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
N/A	0.5642	likely_pathogenic	0.4551	ambiguous	-0.334	Destabilizing	0.927	D	0.558	neutral	None	None	None	None	I
N/C	0.6137	likely_pathogenic	0.515	ambiguous	0.309	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	I
N/D	0.2609	likely_benign	0.1838	benign	0.101	Stabilizing	0.979	D	0.443	neutral	N	0.483616867	None	None	I
N/E	0.6838	likely_pathogenic	0.5237	ambiguous	0.072	Stabilizing	0.969	D	0.414	neutral	None	None	None	None	I
N/F	0.8661	likely_pathogenic	0.7841	pathogenic	-0.691	Destabilizing	0.995	D	0.608	neutral	None	None	None	None	I
N/G	0.277	likely_benign	0.2388	benign	-0.514	Destabilizing	0.013	N	0.19	neutral	None	None	None	None	I
N/H	0.2623	likely_benign	0.1977	benign	-0.5	Destabilizing	0.144	N	0.313	neutral	N	0.514574492	None	None	I
N/I	0.8696	likely_pathogenic	0.7667	pathogenic	0.053	Stabilizing	0.998	D	0.601	neutral	N	0.495437748	None	None	I
N/K	0.7035	likely_pathogenic	0.5134	ambiguous	0.084	Stabilizing	0.979	D	0.454	neutral	N	0.511784903	None	None	I
N/L	0.6592	likely_pathogenic	0.5506	ambiguous	0.053	Stabilizing	0.995	D	0.589	neutral	None	None	None	None	I
N/M	0.7698	likely_pathogenic	0.6731	pathogenic	0.317	Stabilizing	1.0	D	0.589	neutral	None	None	None	None	I
N/P	0.9323	likely_pathogenic	0.9197	pathogenic	-0.049	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	I
N/Q	0.5916	likely_pathogenic	0.4623	ambiguous	-0.361	Destabilizing	0.995	D	0.448	neutral	None	None	None	None	I
N/R	0.721	likely_pathogenic	0.5569	ambiguous	0.148	Stabilizing	0.995	D	0.443	neutral	None	None	None	None	I
N/S	0.1473	likely_benign	0.1296	benign	-0.152	Destabilizing	0.906	D	0.458	neutral	N	0.508128522	None	None	I
N/T	0.4405	ambiguous	0.3405	ambiguous	-0.035	Destabilizing	0.979	D	0.461	neutral	N	0.468179234	None	None	I
N/V	0.8124	likely_pathogenic	0.7032	pathogenic	-0.049	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	I
N/W	0.95	likely_pathogenic	0.92	pathogenic	-0.682	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
N/Y	0.4421	ambiguous	0.3441	ambiguous	-0.412	Destabilizing	0.988	D	0.597	neutral	N	0.494545936	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.