TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14394	43405;43406;43407	chr2:178632951;178632950;178632949	chr2:179497678;179497677;179497676
N2AB	12753	38482;38483;38484	chr2:178632951;178632950;178632949	chr2:179497678;179497677;179497676
N2A	11826	35701;35702;35703	chr2:178632951;178632950;178632949	chr2:179497678;179497677;179497676
N2B	5329	16210;16211;16212	chr2:178632951;178632950;178632949	chr2:179497678;179497677;179497676
Novex-1	5454	16585;16586;16587	chr2:178632951;178632950;178632949	chr2:179497678;179497677;179497676
Novex-2	5521	16786;16787;16788	chr2:178632951;178632950;178632949	chr2:179497678;179497677;179497676
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-94
• Domain position: 76
• Structural Position: 161
• Q(SASA): 0.3614
• 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
N/T	rs1264004420	0.066	0.997	N	0.709	0.452	0.323886383625	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	9.97E-05	0	None	0	None	0	0	0
N/T	rs1264004420	0.066	0.997	N	0.709	0.452	0.323886383625	gnomAD-4.0.0	1.59282E-06	None	None	None	None	N	None	0	0	None	4.77145E-05	0	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	0.6546	likely_pathogenic	0.5912	pathogenic	-0.2	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
N/C	0.8237	likely_pathogenic	0.787	pathogenic	0.29	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
N/D	0.3944	ambiguous	0.3186	benign	0.147	Stabilizing	0.997	D	0.661	prob.neutral	N	0.453434031	None	None	N
N/E	0.8319	likely_pathogenic	0.7864	pathogenic	0.098	Stabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
N/F	0.8791	likely_pathogenic	0.8501	pathogenic	-0.676	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
N/G	0.535	ambiguous	0.4492	ambiguous	-0.338	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	N
N/H	0.3544	ambiguous	0.3165	benign	-0.355	Destabilizing	0.999	D	0.705	prob.delet.	D	0.608257229	None	None	N
N/I	0.7992	likely_pathogenic	0.7466	pathogenic	0.071	Stabilizing	0.999	D	0.723	deleterious	D	0.570150206	None	None	N
N/K	0.8065	likely_pathogenic	0.7389	pathogenic	0.13	Stabilizing	0.999	D	0.725	deleterious	N	0.457552953	None	None	N
N/L	0.7089	likely_pathogenic	0.6549	pathogenic	0.071	Stabilizing	0.999	D	0.636	neutral	None	None	None	None	N
N/M	0.7995	likely_pathogenic	0.7613	pathogenic	0.244	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
N/P	0.9183	likely_pathogenic	0.9043	pathogenic	0.006	Stabilizing	0.999	D	0.697	prob.delet.	None	None	None	None	N
N/Q	0.8	likely_pathogenic	0.7545	pathogenic	-0.267	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
N/R	0.8	likely_pathogenic	0.7491	pathogenic	0.187	Stabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
N/S	0.161	likely_benign	0.1479	benign	-0.04	Destabilizing	0.997	D	0.596	neutral	N	0.446083833	None	None	N
N/T	0.4309	ambiguous	0.3573	ambiguous	0.042	Stabilizing	0.997	D	0.709	prob.delet.	N	0.462192476	None	None	N
N/V	0.7411	likely_pathogenic	0.6962	pathogenic	0.006	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	N
N/W	0.9752	likely_pathogenic	0.9684	pathogenic	-0.737	Destabilizing	1.0	D	0.701	prob.delet.	None	None	None	None	N
N/Y	0.5119	ambiguous	0.4507	ambiguous	-0.438	Destabilizing	1.0	D	0.71	prob.delet.	D	0.608993188	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.