TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22586	67981;67982;67983	chr2:178579274;178579273;178579272	chr2:179444001;179444000;179443999
N2AB	20945	63058;63059;63060	chr2:178579274;178579273;178579272	chr2:179444001;179444000;179443999
N2A	20018	60277;60278;60279	chr2:178579274;178579273;178579272	chr2:179444001;179444000;179443999
N2B	13521	40786;40787;40788	chr2:178579274;178579273;178579272	chr2:179444001;179444000;179443999
Novex-1	13646	41161;41162;41163	chr2:178579274;178579273;178579272	chr2:179444001;179444000;179443999
Novex-2	13713	41362;41363;41364	chr2:178579274;178579273;178579272	chr2:179444001;179444000;179443999
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-127
• Domain position: 27
• Structural Position: 50
• Q(SASA): 0.2431
• 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
K/T	None	None	0.946	N	0.705	0.387	0.413503789086	gnomAD-4.0.0	3.18452E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88402E-05	0	2.86002E-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
K/A	0.8061	likely_pathogenic	0.8291	pathogenic	-0.822	Destabilizing	0.87	D	0.543	neutral	None	None	None	None	N
K/C	0.8419	likely_pathogenic	0.8594	pathogenic	-0.807	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
K/D	0.9307	likely_pathogenic	0.9443	pathogenic	0.214	Stabilizing	0.959	D	0.744	deleterious	None	None	None	None	N
K/E	0.6096	likely_pathogenic	0.6553	pathogenic	0.305	Stabilizing	0.716	D	0.48	neutral	N	0.518752108	None	None	N
K/F	0.8565	likely_pathogenic	0.8757	pathogenic	-0.808	Destabilizing	0.994	D	0.807	deleterious	None	None	None	None	N
K/G	0.9029	likely_pathogenic	0.9183	pathogenic	-1.133	Destabilizing	0.959	D	0.699	prob.neutral	None	None	None	None	N
K/H	0.4427	ambiguous	0.4835	ambiguous	-1.555	Destabilizing	0.994	D	0.782	deleterious	None	None	None	None	N
K/I	0.5575	ambiguous	0.6001	pathogenic	-0.031	Destabilizing	0.973	D	0.814	deleterious	N	0.499380406	None	None	N
K/L	0.56	ambiguous	0.5998	pathogenic	-0.031	Destabilizing	0.959	D	0.699	prob.neutral	None	None	None	None	N
K/M	0.4118	ambiguous	0.4517	ambiguous	-0.023	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
K/N	0.8044	likely_pathogenic	0.8403	pathogenic	-0.273	Destabilizing	0.946	D	0.671	neutral	N	0.507142313	None	None	N
K/P	0.9858	likely_pathogenic	0.9868	pathogenic	-0.266	Destabilizing	0.979	D	0.757	deleterious	None	None	None	None	N
K/Q	0.2971	likely_benign	0.3271	benign	-0.432	Destabilizing	0.946	D	0.656	neutral	N	0.491493594	None	None	N
K/R	0.088	likely_benign	0.0906	benign	-0.442	Destabilizing	0.035	N	0.364	neutral	N	0.489286471	None	None	N
K/S	0.8554	likely_pathogenic	0.8869	pathogenic	-1.084	Destabilizing	0.87	D	0.569	neutral	None	None	None	None	N
K/T	0.6678	likely_pathogenic	0.7019	pathogenic	-0.79	Destabilizing	0.946	D	0.705	prob.neutral	N	0.506888824	None	None	N
K/V	0.5822	likely_pathogenic	0.6191	pathogenic	-0.266	Destabilizing	0.959	D	0.753	deleterious	None	None	None	None	N
K/W	0.8195	likely_pathogenic	0.8426	pathogenic	-0.608	Destabilizing	0.998	D	0.798	deleterious	None	None	None	None	N
K/Y	0.6719	likely_pathogenic	0.7051	pathogenic	-0.287	Destabilizing	0.979	D	0.801	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.