TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2234	6925;6926;6927	chr2:178775011;178775010;178775009	chr2:179639738;179639737;179639736
N2AB	2234	6925;6926;6927	chr2:178775011;178775010;178775009	chr2:179639738;179639737;179639736
N2A	2234	6925;6926;6927	chr2:178775011;178775010;178775009	chr2:179639738;179639737;179639736
N2B	2188	6787;6788;6789	chr2:178775011;178775010;178775009	chr2:179639738;179639737;179639736
Novex-1	2188	6787;6788;6789	chr2:178775011;178775010;178775009	chr2:179639738;179639737;179639736
Novex-2	2188	6787;6788;6789	chr2:178775011;178775010;178775009	chr2:179639738;179639737;179639736
Novex-3	2234	6925;6926;6927	chr2:178775011;178775010;178775009	chr2:179639738;179639737;179639736

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-11
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.1993
• 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
L/M	rs766750289	-1.237	0.999	N	0.711	0.194	0.625654597223	gnomAD-2.1.1	1.59E-05	None	None	None	None	N	None	0	0	None	3.97141E-04	0	None	0	None	0	0	0
L/M	rs766750289	-1.237	0.999	N	0.711	0.194	0.625654597223	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	5.76369E-04	0	None	0	0	0	0	0
L/M	rs766750289	-1.237	0.999	N	0.711	0.194	0.625654597223	gnomAD-4.0.0	4.33727E-06	None	None	None	None	N	None	1.33461E-05	0	None	1.6893E-04	0	None	0	0	8.47485E-07	0	0
L/P	rs534604830	-1.48	0.999	N	0.805	0.613	0.838109445121	gnomAD-2.1.1	7.96E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	8.81E-06	0
L/P	rs534604830	-1.48	0.999	N	0.805	0.613	0.838109445121	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs534604830	-1.48	0.999	N	0.805	0.613	0.838109445121	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
L/P	rs534604830	-1.48	0.999	N	0.805	0.613	0.838109445121	gnomAD-4.0.0	2.56096E-06	None	None	None	None	N	None	0	1.694E-05	None	0	0	None	0	0	2.39202E-06	0	0
L/Q	None	None	0.993	N	0.809	0.451	0.833376837834	gnomAD-4.0.0	1.59084E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
L/A	0.4991	ambiguous	0.5218	ambiguous	-1.986	Destabilizing	0.983	D	0.559	neutral	None	None	None	None	N
L/C	0.7638	likely_pathogenic	0.7705	pathogenic	-1.347	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
L/D	0.8983	likely_pathogenic	0.9056	pathogenic	-1.408	Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	N
L/E	0.6597	likely_pathogenic	0.6785	pathogenic	-1.348	Destabilizing	0.995	D	0.793	deleterious	None	None	None	None	N
L/F	0.2256	likely_benign	0.2471	benign	-1.345	Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
L/G	0.7511	likely_pathogenic	0.7659	pathogenic	-2.373	Highly Destabilizing	0.995	D	0.792	deleterious	None	None	None	None	N
L/H	0.4321	ambiguous	0.4496	ambiguous	-1.573	Destabilizing	0.483	N	0.505	neutral	None	None	None	None	N
L/I	0.1509	likely_benign	0.1596	benign	-0.961	Destabilizing	0.991	D	0.472	neutral	None	None	None	None	N
L/K	0.4699	ambiguous	0.4863	ambiguous	-1.267	Destabilizing	0.995	D	0.787	deleterious	None	None	None	None	N
L/M	0.1556	likely_benign	0.1672	benign	-0.808	Destabilizing	0.999	D	0.711	prob.delet.	N	0.509555358	None	None	N
L/N	0.5806	likely_pathogenic	0.6032	pathogenic	-1.17	Destabilizing	0.995	D	0.805	deleterious	None	None	None	None	N
L/P	0.7984	likely_pathogenic	0.8209	pathogenic	-1.274	Destabilizing	0.999	D	0.805	deleterious	N	0.510625754	None	None	N
L/Q	0.2994	likely_benign	0.3152	benign	-1.295	Destabilizing	0.993	D	0.809	deleterious	N	0.504454236	None	None	N
L/R	0.3747	ambiguous	0.3885	ambiguous	-0.762	Destabilizing	0.993	D	0.803	deleterious	N	0.472341843	None	None	N
L/S	0.5129	ambiguous	0.5335	ambiguous	-1.909	Destabilizing	0.995	D	0.778	deleterious	None	None	None	None	N
L/T	0.4012	ambiguous	0.4155	ambiguous	-1.725	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
L/V	0.168	likely_benign	0.1775	benign	-1.274	Destabilizing	0.989	D	0.433	neutral	N	0.505958288	None	None	N
L/W	0.4908	ambiguous	0.5375	ambiguous	-1.452	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/Y	0.5625	ambiguous	0.5994	pathogenic	-1.215	Destabilizing	0.995	D	0.808	deleterious	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.