TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8074	24445;24446;24447	chr2:178719170;178719169;178719168	chr2:179583897;179583896;179583895
N2AB	7757	23494;23495;23496	chr2:178719170;178719169;178719168	chr2:179583897;179583896;179583895
N2A	6830	20713;20714;20715	chr2:178719170;178719169;178719168	chr2:179583897;179583896;179583895
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-65
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.4455
• 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
V/E	None	None	0.781	D	0.71	0.826	0.902821803296	gnomAD-4.0.0	1.59873E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43649E-05	0
V/L	None	None	0.034	D	0.633	0.477	0.597125599913	gnomAD-4.0.0	1.3712E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.01247E-07	1.16271E-05	0
V/M	rs763504178	-0.532	0.638	D	0.725	0.57	0.747430590049	gnomAD-2.1.1	1.63E-05	None	None	None	None	I	None	0	1.16218E-04	None	0	0	None	0	None	0	0	0
V/M	rs763504178	-0.532	0.638	D	0.725	0.57	0.747430590049	gnomAD-4.0.0	2.7424E-06	None	None	None	None	I	None	0	8.95696E-05	None	0	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
V/A	0.5429	ambiguous	0.549	ambiguous	-1.836	Destabilizing	0.334	N	0.608	neutral	D	0.64869974	None	None	I
V/C	0.9212	likely_pathogenic	0.9342	pathogenic	-1.703	Destabilizing	0.982	D	0.709	prob.delet.	None	None	None	None	I
V/D	0.9692	likely_pathogenic	0.9764	pathogenic	-2.567	Highly Destabilizing	0.826	D	0.739	prob.delet.	None	None	None	None	I
V/E	0.9132	likely_pathogenic	0.9253	pathogenic	-2.514	Highly Destabilizing	0.781	D	0.71	prob.delet.	D	0.649305153	None	None	I
V/F	0.5177	ambiguous	0.6057	pathogenic	-1.426	Destabilizing	0.7	D	0.697	prob.neutral	None	None	None	None	I
V/G	0.7569	likely_pathogenic	0.7579	pathogenic	-2.194	Highly Destabilizing	0.781	D	0.714	prob.delet.	D	0.649305153	None	None	I
V/H	0.9656	likely_pathogenic	0.9764	pathogenic	-1.738	Destabilizing	0.982	D	0.739	prob.delet.	None	None	None	None	I
V/I	0.0707	likely_benign	0.0873	benign	-0.911	Destabilizing	0.002	N	0.489	neutral	None	None	None	None	I
V/K	0.9199	likely_pathogenic	0.9359	pathogenic	-1.548	Destabilizing	0.826	D	0.711	prob.delet.	None	None	None	None	I
V/L	0.2816	likely_benign	0.3737	ambiguous	-0.911	Destabilizing	0.034	N	0.633	neutral	D	0.595605474	None	None	I
V/M	0.2866	likely_benign	0.3531	ambiguous	-0.917	Destabilizing	0.638	D	0.725	prob.delet.	D	0.623363433	None	None	I
V/N	0.8713	likely_pathogenic	0.9106	pathogenic	-1.602	Destabilizing	0.935	D	0.747	deleterious	None	None	None	None	I
V/P	0.8732	likely_pathogenic	0.8887	pathogenic	-1.189	Destabilizing	0.935	D	0.721	prob.delet.	None	None	None	None	I
V/Q	0.8996	likely_pathogenic	0.9176	pathogenic	-1.755	Destabilizing	0.935	D	0.732	prob.delet.	None	None	None	None	I
V/R	0.8851	likely_pathogenic	0.8991	pathogenic	-1.074	Destabilizing	0.826	D	0.745	deleterious	None	None	None	None	I
V/S	0.735	likely_pathogenic	0.7614	pathogenic	-2.093	Highly Destabilizing	0.826	D	0.683	prob.neutral	None	None	None	None	I
V/T	0.5843	likely_pathogenic	0.6157	pathogenic	-1.931	Destabilizing	0.399	N	0.672	neutral	None	None	None	None	I
V/W	0.9754	likely_pathogenic	0.9842	pathogenic	-1.709	Destabilizing	0.982	D	0.711	prob.delet.	None	None	None	None	I
V/Y	0.9216	likely_pathogenic	0.9493	pathogenic	-1.39	Destabilizing	0.826	D	0.703	prob.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.