TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21671	65236;65237;65238	chr2:178584540;178584539;178584538	chr2:179449267;179449266;179449265
N2AB	20030	60313;60314;60315	chr2:178584540;178584539;178584538	chr2:179449267;179449266;179449265
N2A	19103	57532;57533;57534	chr2:178584540;178584539;178584538	chr2:179449267;179449266;179449265
N2B	12606	38041;38042;38043	chr2:178584540;178584539;178584538	chr2:179449267;179449266;179449265
Novex-1	12731	38416;38417;38418	chr2:178584540;178584539;178584538	chr2:179449267;179449266;179449265
Novex-2	12798	38617;38618;38619	chr2:178584540;178584539;178584538	chr2:179449267;179449266;179449265
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-45
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2405
• 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/I	rs764854284	-0.688	0.543	N	0.214	0.202	0.309530620856	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.56E-05	None	0	8.9E-06	0
V/I	rs764854284	-0.688	0.543	N	0.214	0.202	0.309530620856	gnomAD-4.0.0	1.27495E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14512E-05	5.7374E-05	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	0.3537	ambiguous	0.377	ambiguous	-1.882	Destabilizing	0.994	D	0.421	neutral	N	0.462668378	None	None	N
V/C	0.7924	likely_pathogenic	0.7966	pathogenic	-1.418	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/D	0.8352	likely_pathogenic	0.8615	pathogenic	-2.357	Highly Destabilizing	0.999	D	0.795	deleterious	N	0.500036559	None	None	N
V/E	0.666	likely_pathogenic	0.6705	pathogenic	-2.264	Highly Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
V/F	0.4624	ambiguous	0.4533	ambiguous	-1.272	Destabilizing	0.998	D	0.732	prob.delet.	N	0.47480596	None	None	N
V/G	0.4663	ambiguous	0.4911	ambiguous	-2.3	Highly Destabilizing	0.999	D	0.785	deleterious	N	0.512406822	None	None	N
V/H	0.8814	likely_pathogenic	0.8784	pathogenic	-2.015	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
V/I	0.0949	likely_benign	0.0932	benign	-0.775	Destabilizing	0.543	D	0.214	neutral	N	0.434113553	None	None	N
V/K	0.7346	likely_pathogenic	0.7316	pathogenic	-1.611	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
V/L	0.5248	ambiguous	0.5174	ambiguous	-0.775	Destabilizing	0.948	D	0.315	neutral	N	0.516385433	None	None	N
V/M	0.3149	likely_benign	0.3253	benign	-0.697	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
V/N	0.6607	likely_pathogenic	0.6816	pathogenic	-1.611	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/P	0.8532	likely_pathogenic	0.8831	pathogenic	-1.113	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/Q	0.6399	likely_pathogenic	0.6238	pathogenic	-1.66	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
V/R	0.6837	likely_pathogenic	0.6686	pathogenic	-1.234	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
V/S	0.4998	ambiguous	0.5293	ambiguous	-2.144	Highly Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
V/T	0.3582	ambiguous	0.3632	ambiguous	-1.938	Destabilizing	0.996	D	0.525	neutral	None	None	None	None	N
V/W	0.934	likely_pathogenic	0.9345	pathogenic	-1.668	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/Y	0.7973	likely_pathogenic	0.8026	pathogenic	-1.341	Destabilizing	1.0	D	0.753	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.