TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19641	59146;59147;59148	chr2:178593287;178593286;178593285	chr2:179458014;179458013;179458012
N2AB	18000	54223;54224;54225	chr2:178593287;178593286;178593285	chr2:179458014;179458013;179458012
N2A	17073	51442;51443;51444	chr2:178593287;178593286;178593285	chr2:179458014;179458013;179458012
N2B	10576	31951;31952;31953	chr2:178593287;178593286;178593285	chr2:179458014;179458013;179458012
Novex-1	10701	32326;32327;32328	chr2:178593287;178593286;178593285	chr2:179458014;179458013;179458012
Novex-2	10768	32527;32528;32529	chr2:178593287;178593286;178593285	chr2:179458014;179458013;179458012
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-30
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1152
• 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/A	None	None	0.892	N	0.659	0.332	0.628610474668	gnomAD-4.0.0	1.20036E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31254E-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
V/A	0.6684	likely_pathogenic	0.677	pathogenic	-1.882	Destabilizing	0.892	D	0.659	neutral	N	0.479809618	None	None	N
V/C	0.8822	likely_pathogenic	0.8989	pathogenic	-1.439	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
V/D	0.9895	likely_pathogenic	0.9891	pathogenic	-2.892	Highly Destabilizing	0.994	D	0.871	deleterious	D	0.528197354	None	None	N
V/E	0.9724	likely_pathogenic	0.9714	pathogenic	-2.584	Highly Destabilizing	0.996	D	0.868	deleterious	None	None	None	None	N
V/F	0.8133	likely_pathogenic	0.8073	pathogenic	-1.081	Destabilizing	0.056	N	0.559	neutral	N	0.504582462	None	None	N
V/G	0.8706	likely_pathogenic	0.8808	pathogenic	-2.491	Highly Destabilizing	0.983	D	0.867	deleterious	D	0.551835017	None	None	N
V/H	0.9906	likely_pathogenic	0.9906	pathogenic	-2.482	Highly Destabilizing	0.999	D	0.89	deleterious	None	None	None	None	N
V/I	0.121	likely_benign	0.1101	benign	-0.134	Destabilizing	0.63	D	0.549	neutral	N	0.496530236	None	None	N
V/K	0.9857	likely_pathogenic	0.9856	pathogenic	-1.626	Destabilizing	0.987	D	0.863	deleterious	None	None	None	None	N
V/L	0.6453	likely_pathogenic	0.6203	pathogenic	-0.134	Destabilizing	0.63	D	0.66	neutral	N	0.467859611	None	None	N
V/M	0.669	likely_pathogenic	0.6369	pathogenic	-0.32	Destabilizing	0.987	D	0.74	deleterious	None	None	None	None	N
V/N	0.9659	likely_pathogenic	0.9672	pathogenic	-2.251	Highly Destabilizing	0.996	D	0.891	deleterious	None	None	None	None	N
V/P	0.9785	likely_pathogenic	0.9802	pathogenic	-0.694	Destabilizing	0.996	D	0.865	deleterious	None	None	None	None	N
V/Q	0.971	likely_pathogenic	0.9715	pathogenic	-1.91	Destabilizing	0.996	D	0.897	deleterious	None	None	None	None	N
V/R	0.9806	likely_pathogenic	0.9805	pathogenic	-1.791	Destabilizing	0.996	D	0.9	deleterious	None	None	None	None	N
V/S	0.8638	likely_pathogenic	0.8762	pathogenic	-2.795	Highly Destabilizing	0.987	D	0.861	deleterious	None	None	None	None	N
V/T	0.7987	likely_pathogenic	0.8096	pathogenic	-2.315	Highly Destabilizing	0.957	D	0.705	prob.neutral	None	None	None	None	N
V/W	0.9961	likely_pathogenic	0.9958	pathogenic	-1.685	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
V/Y	0.9757	likely_pathogenic	0.9764	pathogenic	-1.236	Destabilizing	0.95	D	0.813	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.