TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24883	74872;74873;74874	chr2:178571485;178571484;178571483	chr2:179436212;179436211;179436210
N2AB	23242	69949;69950;69951	chr2:178571485;178571484;178571483	chr2:179436212;179436211;179436210
N2A	22315	67168;67169;67170	chr2:178571485;178571484;178571483	chr2:179436212;179436211;179436210
N2B	15818	47677;47678;47679	chr2:178571485;178571484;178571483	chr2:179436212;179436211;179436210
Novex-1	15943	48052;48053;48054	chr2:178571485;178571484;178571483	chr2:179436212;179436211;179436210
Novex-2	16010	48253;48254;48255	chr2:178571485;178571484;178571483	chr2:179436212;179436211;179436210
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-68
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0555
• 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/T	rs1191756557	-3.492	0.892	N	0.671	0.556	0.696609645563	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
I/T	rs1191756557	-3.492	0.892	N	0.671	0.556	0.696609645563	gnomAD-4.0.0	2.05317E-06	None	None	None	None	N	None	0	0	None	0	2.52793E-05	None	0	0	8.99606E-07	0	1.65728E-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
I/A	0.9442	likely_pathogenic	0.9346	pathogenic	-3.142	Highly Destabilizing	0.845	D	0.649	neutral	None	None	None	None	N
I/C	0.9749	likely_pathogenic	0.9704	pathogenic	-2.2	Highly Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
I/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.827	Highly Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
I/E	0.9983	likely_pathogenic	0.9982	pathogenic	-3.519	Highly Destabilizing	0.987	D	0.865	deleterious	None	None	None	None	N
I/F	0.8781	likely_pathogenic	0.8414	pathogenic	-1.965	Destabilizing	0.967	D	0.573	neutral	N	0.511116602	None	None	N
I/G	0.9968	likely_pathogenic	0.996	pathogenic	-3.704	Highly Destabilizing	0.987	D	0.86	deleterious	None	None	None	None	N
I/H	0.999	likely_pathogenic	0.9989	pathogenic	-3.283	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
I/K	0.9974	likely_pathogenic	0.9974	pathogenic	-2.55	Highly Destabilizing	0.987	D	0.867	deleterious	None	None	None	None	N
I/L	0.6027	likely_pathogenic	0.5711	pathogenic	-1.426	Destabilizing	0.426	N	0.277	neutral	N	0.476612705	None	None	N
I/M	0.6584	likely_pathogenic	0.6159	pathogenic	-1.523	Destabilizing	0.983	D	0.6	neutral	N	0.502976301	None	None	N
I/N	0.9951	likely_pathogenic	0.9949	pathogenic	-3.261	Highly Destabilizing	0.994	D	0.885	deleterious	D	0.529981326	None	None	N
I/P	0.9975	likely_pathogenic	0.9968	pathogenic	-1.994	Destabilizing	0.996	D	0.887	deleterious	None	None	None	None	N
I/Q	0.9977	likely_pathogenic	0.9976	pathogenic	-2.941	Highly Destabilizing	0.996	D	0.888	deleterious	None	None	None	None	N
I/R	0.9955	likely_pathogenic	0.9955	pathogenic	-2.482	Highly Destabilizing	0.987	D	0.886	deleterious	None	None	None	None	N
I/S	0.9846	likely_pathogenic	0.9833	pathogenic	-3.75	Highly Destabilizing	0.983	D	0.807	deleterious	N	0.518460436	None	None	N
I/T	0.9467	likely_pathogenic	0.9403	pathogenic	-3.296	Highly Destabilizing	0.892	D	0.671	neutral	N	0.50322979	None	None	N
I/V	0.1015	likely_benign	0.1019	benign	-1.994	Destabilizing	0.011	N	0.191	neutral	N	0.386878888	None	None	N
I/W	0.9986	likely_pathogenic	0.9978	pathogenic	-2.323	Highly Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
I/Y	0.9927	likely_pathogenic	0.991	pathogenic	-2.207	Highly Destabilizing	0.987	D	0.707	prob.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.