TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5882	17869;17870;17871	chr2:178731021;178731020;178731019	chr2:179595748;179595747;179595746
N2AB	5565	16918;16919;16920	chr2:178731021;178731020;178731019	chr2:179595748;179595747;179595746
N2A	4638	14137;14138;14139	chr2:178731021;178731020;178731019	chr2:179595748;179595747;179595746
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-42
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0807
• 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	rs763665430	-3.363	0.939	D	0.753	0.793	0.831353130882	gnomAD-2.1.1	6.42E-05	None	None	None	None	N	None	0	5.0954E-04	None	0	0	None	0	None	0	0	0
I/T	rs763665430	-3.363	0.939	D	0.753	0.793	0.831353130882	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.31079E-04	0	0	0	None	0	0	0	0	0
I/T	rs763665430	-3.363	0.939	D	0.753	0.793	0.831353130882	gnomAD-4.0.0	2.69097E-05	None	None	None	None	N	None	0	3.55993E-04	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	0.9204	likely_pathogenic	0.9568	pathogenic	-2.921	Highly Destabilizing	0.91	D	0.698	prob.neutral	None	None	None	None	N
I/C	0.9174	likely_pathogenic	0.9486	pathogenic	-2.274	Highly Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
I/D	0.9887	likely_pathogenic	0.995	pathogenic	-3.421	Highly Destabilizing	0.998	D	0.876	deleterious	None	None	None	None	N
I/E	0.9793	likely_pathogenic	0.9902	pathogenic	-3.149	Highly Destabilizing	0.993	D	0.876	deleterious	None	None	None	None	N
I/F	0.3666	ambiguous	0.4863	ambiguous	-1.727	Destabilizing	0.991	D	0.717	prob.delet.	D	0.55832697	None	None	N
I/G	0.9762	likely_pathogenic	0.9884	pathogenic	-3.509	Highly Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
I/H	0.9594	likely_pathogenic	0.9785	pathogenic	-2.991	Highly Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
I/K	0.956	likely_pathogenic	0.9762	pathogenic	-2.318	Highly Destabilizing	0.993	D	0.875	deleterious	None	None	None	None	N
I/L	0.2015	likely_benign	0.2262	benign	-1.185	Destabilizing	0.58	D	0.377	neutral	D	0.580311591	None	None	N
I/M	0.1788	likely_benign	0.2079	benign	-1.256	Destabilizing	0.991	D	0.692	prob.neutral	D	0.59530187	None	None	N
I/N	0.8695	likely_pathogenic	0.9256	pathogenic	-2.817	Highly Destabilizing	0.997	D	0.887	deleterious	D	0.622252612	None	None	N
I/P	0.9927	likely_pathogenic	0.9958	pathogenic	-1.749	Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
I/Q	0.9634	likely_pathogenic	0.9804	pathogenic	-2.595	Highly Destabilizing	0.998	D	0.901	deleterious	None	None	None	None	N
I/R	0.9432	likely_pathogenic	0.9711	pathogenic	-2.079	Highly Destabilizing	0.993	D	0.896	deleterious	None	None	None	None	N
I/S	0.9277	likely_pathogenic	0.9646	pathogenic	-3.499	Highly Destabilizing	0.991	D	0.841	deleterious	D	0.622252612	None	None	N
I/T	0.9278	likely_pathogenic	0.9669	pathogenic	-3.074	Highly Destabilizing	0.939	D	0.753	deleterious	D	0.584470494	None	None	N
I/V	0.129	likely_benign	0.1537	benign	-1.749	Destabilizing	0.02	N	0.246	neutral	D	0.55152455	None	None	N
I/W	0.9529	likely_pathogenic	0.9708	pathogenic	-2.159	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
I/Y	0.834	likely_pathogenic	0.8924	pathogenic	-1.928	Destabilizing	0.998	D	0.781	deleterious	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.