TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15247	45964;45965;45966	chr2:178620871;178620870;178620869	chr2:179485598;179485597;179485596
N2AB	13606	41041;41042;41043	chr2:178620871;178620870;178620869	chr2:179485598;179485597;179485596
N2A	12679	38260;38261;38262	chr2:178620871;178620870;178620869	chr2:179485598;179485597;179485596
N2B	6182	18769;18770;18771	chr2:178620871;178620870;178620869	chr2:179485598;179485597;179485596
Novex-1	6307	19144;19145;19146	chr2:178620871;178620870;178620869	chr2:179485598;179485597;179485596
Novex-2	6374	19345;19346;19347	chr2:178620871;178620870;178620869	chr2:179485598;179485597;179485596
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-104
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.1724
• 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/L	rs373857517	-0.493	0.031	N	0.181	0.106	0.301122078929	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.93E-05	0
I/L	rs373857517	-0.493	0.031	N	0.181	0.106	0.301122078929	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	7.36E-05	0	0
I/L	rs373857517	-0.493	0.031	N	0.181	0.106	0.301122078929	gnomAD-4.0.0	2.72867E-05	None	None	None	None	N	None	1.3369E-05	0	None	0	0	None	0	0	3.5619E-05	0	1.60277E-05
I/M	None	None	0.989	D	0.495	0.402	0.476445137733	gnomAD-4.0.0	1.59365E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86252E-06	0	0
I/T	rs2058158687	None	0.98	D	0.538	0.645	0.704871065003	gnomAD-4.0.0	4.79251E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39935E-06	1.15982E-05	0
I/V	rs373857517	-1.156	0.689	N	0.409	0.213	0.52515372042	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
I/V	rs373857517	-1.156	0.689	N	0.409	0.213	0.52515372042	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs373857517	-1.156	0.689	N	0.409	0.213	0.52515372042	gnomAD-4.0.0	2.63345E-05	None	None	None	None	N	None	9.66277E-05	0	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
I/A	0.8657	likely_pathogenic	0.871	pathogenic	-1.778	Destabilizing	0.985	D	0.468	neutral	None	None	None	None	N
I/C	0.947	likely_pathogenic	0.9543	pathogenic	-0.855	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	N
I/D	0.9926	likely_pathogenic	0.9912	pathogenic	-2.17	Highly Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
I/E	0.9861	likely_pathogenic	0.9835	pathogenic	-1.916	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
I/F	0.5154	ambiguous	0.5475	ambiguous	-1.185	Destabilizing	0.991	D	0.479	neutral	None	None	None	None	N
I/G	0.9811	likely_pathogenic	0.9816	pathogenic	-2.258	Highly Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
I/H	0.9737	likely_pathogenic	0.9743	pathogenic	-1.852	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
I/K	0.965	likely_pathogenic	0.9629	pathogenic	-1.152	Destabilizing	0.998	D	0.701	prob.neutral	D	0.670520522	None	None	N
I/L	0.1635	likely_benign	0.1788	benign	-0.373	Destabilizing	0.031	N	0.181	neutral	N	0.480193388	None	None	N
I/M	0.2653	likely_benign	0.2832	benign	-0.349	Destabilizing	0.989	D	0.495	neutral	D	0.565022999	None	None	N
I/N	0.9271	likely_pathogenic	0.9204	pathogenic	-1.666	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
I/P	0.9799	likely_pathogenic	0.9762	pathogenic	-0.827	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
I/Q	0.9672	likely_pathogenic	0.9654	pathogenic	-1.416	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
I/R	0.9404	likely_pathogenic	0.9354	pathogenic	-1.244	Destabilizing	0.998	D	0.732	prob.delet.	D	0.670520522	None	None	N
I/S	0.913	likely_pathogenic	0.9045	pathogenic	-2.213	Highly Destabilizing	0.999	D	0.608	neutral	None	None	None	None	N
I/T	0.8728	likely_pathogenic	0.8646	pathogenic	-1.811	Destabilizing	0.98	D	0.538	neutral	D	0.665185034	None	None	N
I/V	0.106	likely_benign	0.1195	benign	-0.827	Destabilizing	0.689	D	0.409	neutral	N	0.502095653	None	None	N
I/W	0.9804	likely_pathogenic	0.9822	pathogenic	-1.519	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
I/Y	0.9176	likely_pathogenic	0.9216	pathogenic	-1.15	Destabilizing	0.999	D	0.624	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.