TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22676	68251;68252;68253	chr2:178579004;178579003;178579002	chr2:179443731;179443730;179443729
N2AB	21035	63328;63329;63330	chr2:178579004;178579003;178579002	chr2:179443731;179443730;179443729
N2A	20108	60547;60548;60549	chr2:178579004;178579003;178579002	chr2:179443731;179443730;179443729
N2B	13611	41056;41057;41058	chr2:178579004;178579003;178579002	chr2:179443731;179443730;179443729
Novex-1	13736	41431;41432;41433	chr2:178579004;178579003;178579002	chr2:179443731;179443730;179443729
Novex-2	13803	41632;41633;41634	chr2:178579004;178579003;178579002	chr2:179443731;179443730;179443729
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-52
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.1743
• 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
I/N	None	None	0.99	N	0.837	0.585	0.852610865174	gnomAD-4.0.0	1.59246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86018E-06	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
I/A	0.9805	likely_pathogenic	0.9798	pathogenic	-2.335	Highly Destabilizing	0.559	D	0.593	neutral	None	None	None	None	N
I/C	0.9853	likely_pathogenic	0.985	pathogenic	-1.471	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
I/D	0.9982	likely_pathogenic	0.9979	pathogenic	-2.353	Highly Destabilizing	0.993	D	0.823	deleterious	None	None	None	None	N
I/E	0.9941	likely_pathogenic	0.9936	pathogenic	-2.3	Highly Destabilizing	0.978	D	0.818	deleterious	None	None	None	None	N
I/F	0.9538	likely_pathogenic	0.9358	pathogenic	-1.739	Destabilizing	0.942	D	0.659	neutral	N	0.510711755	None	None	N
I/G	0.996	likely_pathogenic	0.9958	pathogenic	-2.732	Highly Destabilizing	0.978	D	0.817	deleterious	None	None	None	None	N
I/H	0.9975	likely_pathogenic	0.9965	pathogenic	-2.025	Highly Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
I/K	0.9884	likely_pathogenic	0.9848	pathogenic	-1.706	Destabilizing	0.978	D	0.818	deleterious	None	None	None	None	N
I/L	0.5425	ambiguous	0.5432	ambiguous	-1.259	Destabilizing	0.294	N	0.337	neutral	D	0.524738344	None	None	N
I/M	0.6284	likely_pathogenic	0.5667	pathogenic	-0.864	Destabilizing	0.97	D	0.648	neutral	D	0.531350906	None	None	N
I/N	0.9673	likely_pathogenic	0.9612	pathogenic	-1.629	Destabilizing	0.99	D	0.837	deleterious	N	0.520843974	None	None	N
I/P	0.9731	likely_pathogenic	0.9739	pathogenic	-1.592	Destabilizing	0.993	D	0.83	deleterious	None	None	None	None	N
I/Q	0.9942	likely_pathogenic	0.9926	pathogenic	-1.782	Destabilizing	0.993	D	0.833	deleterious	None	None	None	None	N
I/R	0.9891	likely_pathogenic	0.9863	pathogenic	-1.073	Destabilizing	0.978	D	0.835	deleterious	None	None	None	None	N
I/S	0.9846	likely_pathogenic	0.9836	pathogenic	-2.243	Highly Destabilizing	0.97	D	0.777	deleterious	N	0.51350014	None	None	N
I/T	0.9563	likely_pathogenic	0.9504	pathogenic	-2.069	Highly Destabilizing	0.822	D	0.664	neutral	N	0.499510489	None	None	N
I/V	0.1325	likely_benign	0.137	benign	-1.592	Destabilizing	0.002	N	0.153	neutral	N	0.454376969	None	None	N
I/W	0.9986	likely_pathogenic	0.9978	pathogenic	-1.933	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
I/Y	0.9909	likely_pathogenic	0.9889	pathogenic	-1.721	Destabilizing	0.978	D	0.721	prob.delet.	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.