TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22390	67393;67394;67395	chr2:178580119;178580118;178580117	chr2:179444846;179444845;179444844
N2AB	20749	62470;62471;62472	chr2:178580119;178580118;178580117	chr2:179444846;179444845;179444844
N2A	19822	59689;59690;59691	chr2:178580119;178580118;178580117	chr2:179444846;179444845;179444844
N2B	13325	40198;40199;40200	chr2:178580119;178580118;178580117	chr2:179444846;179444845;179444844
Novex-1	13450	40573;40574;40575	chr2:178580119;178580118;178580117	chr2:179444846;179444845;179444844
Novex-2	13517	40774;40775;40776	chr2:178580119;178580118;178580117	chr2:179444846;179444845;179444844
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-50
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1342
• 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
V/L	None	None	0.247	N	0.493	0.187	0.495506531988	gnomAD-4.0.0	6.84382E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99672E-07	0	0
V/M	rs778578056	-1.226	0.942	N	0.759	0.256	0.596538173739	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/M	rs778578056	-1.226	0.942	N	0.759	0.256	0.596538173739	gnomAD-4.0.0	6.84382E-07	None	None	None	None	N	None	2.99097E-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
V/A	0.5995	likely_pathogenic	0.5737	pathogenic	-2.306	Highly Destabilizing	0.822	D	0.617	neutral	N	0.474545109	None	None	N
V/C	0.8634	likely_pathogenic	0.828	pathogenic	-2.134	Highly Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
V/D	0.9103	likely_pathogenic	0.9013	pathogenic	-3.254	Highly Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	N
V/E	0.7625	likely_pathogenic	0.7554	pathogenic	-3.042	Highly Destabilizing	0.99	D	0.727	prob.delet.	N	0.511011325	None	None	N
V/F	0.482	ambiguous	0.4764	ambiguous	-1.317	Destabilizing	0.956	D	0.749	deleterious	None	None	None	None	N
V/G	0.7951	likely_pathogenic	0.7892	pathogenic	-2.817	Highly Destabilizing	0.971	D	0.765	deleterious	N	0.502310602	None	None	N
V/H	0.8463	likely_pathogenic	0.8119	pathogenic	-2.467	Highly Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
V/I	0.0813	likely_benign	0.0731	benign	-0.872	Destabilizing	0.019	N	0.245	neutral	None	None	None	None	N
V/K	0.7622	likely_pathogenic	0.757	pathogenic	-1.912	Destabilizing	0.978	D	0.739	prob.delet.	None	None	None	None	N
V/L	0.4096	ambiguous	0.3867	ambiguous	-0.872	Destabilizing	0.247	N	0.493	neutral	N	0.467820695	None	None	N
V/M	0.3389	likely_benign	0.3004	benign	-1.153	Destabilizing	0.942	D	0.759	deleterious	N	0.477876471	None	None	N
V/N	0.7857	likely_pathogenic	0.7442	pathogenic	-2.306	Highly Destabilizing	0.993	D	0.807	deleterious	None	None	None	None	N
V/P	0.9949	likely_pathogenic	0.9943	pathogenic	-1.326	Destabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
V/Q	0.73	likely_pathogenic	0.711	pathogenic	-2.167	Highly Destabilizing	0.993	D	0.776	deleterious	None	None	None	None	N
V/R	0.6462	likely_pathogenic	0.6643	pathogenic	-1.686	Destabilizing	0.993	D	0.806	deleterious	None	None	None	None	N
V/S	0.701	likely_pathogenic	0.6526	pathogenic	-2.865	Highly Destabilizing	0.978	D	0.735	prob.delet.	None	None	None	None	N
V/T	0.4245	ambiguous	0.3774	ambiguous	-2.521	Highly Destabilizing	0.86	D	0.716	prob.delet.	None	None	None	None	N
V/W	0.9526	likely_pathogenic	0.9471	pathogenic	-1.832	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
V/Y	0.8304	likely_pathogenic	0.8181	pathogenic	-1.522	Destabilizing	0.978	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.