TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7764	23515;23516;23517	chr2:178720472;178720471;178720470	chr2:179585199;179585198;179585197
N2AB	7447	22564;22565;22566	chr2:178720472;178720471;178720470	chr2:179585199;179585198;179585197
N2A	6520	19783;19784;19785	chr2:178720472;178720471;178720470	chr2:179585199;179585198;179585197
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-62
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1132
• 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/I	None	None	0.027	N	0.485	0.049	0.256283259241	gnomAD-4.0.0	1.59156E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	0
L/P	rs1413753534	-2.22	0.741	N	0.654	0.42	0.824210825843	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
L/P	rs1413753534	-2.22	0.741	N	0.654	0.42	0.824210825843	gnomAD-4.0.0	1.36852E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99538E-07	0	1.65678E-05

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	0.5748	likely_pathogenic	0.5942	pathogenic	-2.773	Highly Destabilizing	0.035	N	0.47	neutral	None	None	None	None	N
L/C	0.7674	likely_pathogenic	0.7608	pathogenic	-2.812	Highly Destabilizing	0.001	N	0.362	neutral	None	None	None	None	N
L/D	0.9933	likely_pathogenic	0.9933	pathogenic	-3.684	Highly Destabilizing	0.235	N	0.644	neutral	None	None	None	None	N
L/E	0.9632	likely_pathogenic	0.9641	pathogenic	-3.498	Highly Destabilizing	0.38	N	0.645	neutral	None	None	None	None	N
L/F	0.3759	ambiguous	0.4023	ambiguous	-1.705	Destabilizing	0.001	N	0.358	neutral	N	0.494714587	None	None	N
L/G	0.9252	likely_pathogenic	0.9329	pathogenic	-3.253	Highly Destabilizing	0.149	N	0.604	neutral	None	None	None	None	N
L/H	0.9157	likely_pathogenic	0.9185	pathogenic	-2.534	Highly Destabilizing	0.78	D	0.61	neutral	D	0.525107752	None	None	N
L/I	0.1096	likely_benign	0.1122	benign	-1.385	Destabilizing	0.027	N	0.485	neutral	N	0.480144992	None	None	N
L/K	0.9611	likely_pathogenic	0.9627	pathogenic	-2.275	Highly Destabilizing	0.38	N	0.617	neutral	None	None	None	None	N
L/M	0.1579	likely_benign	0.1703	benign	-1.67	Destabilizing	0.555	D	0.566	neutral	None	None	None	None	N
L/N	0.9401	likely_pathogenic	0.9426	pathogenic	-2.714	Highly Destabilizing	0.005	N	0.453	neutral	None	None	None	None	N
L/P	0.8771	likely_pathogenic	0.8957	pathogenic	-1.832	Destabilizing	0.741	D	0.654	neutral	N	0.521997188	None	None	N
L/Q	0.8529	likely_pathogenic	0.8647	pathogenic	-2.656	Highly Destabilizing	0.555	D	0.615	neutral	None	None	None	None	N
L/R	0.9302	likely_pathogenic	0.9325	pathogenic	-1.854	Destabilizing	0.484	N	0.617	neutral	D	0.525107752	None	None	N
L/S	0.8231	likely_pathogenic	0.819	pathogenic	-3.327	Highly Destabilizing	0.149	N	0.535	neutral	None	None	None	None	N
L/T	0.4545	ambiguous	0.4588	ambiguous	-3.005	Highly Destabilizing	0.149	N	0.517	neutral	None	None	None	None	N
L/V	0.0996	likely_benign	0.1032	benign	-1.832	Destabilizing	None	N	0.217	neutral	N	0.386597326	None	None	N
L/W	0.8189	likely_pathogenic	0.8273	pathogenic	-2.04	Highly Destabilizing	0.824	D	0.546	neutral	None	None	None	None	N
L/Y	0.8826	likely_pathogenic	0.896	pathogenic	-1.858	Destabilizing	0.235	N	0.623	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.