TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13780	41563;41564;41565	chr2:178636233;178636232;178636231	chr2:179500960;179500959;179500958
N2AB	12139	36640;36641;36642	chr2:178636233;178636232;178636231	chr2:179500960;179500959;179500958
N2A	11212	33859;33860;33861	chr2:178636233;178636232;178636231	chr2:179500960;179500959;179500958
N2B	4715	14368;14369;14370	chr2:178636233;178636232;178636231	chr2:179500960;179500959;179500958
Novex-1	4840	14743;14744;14745	chr2:178636233;178636232;178636231	chr2:179500960;179500959;179500958
Novex-2	4907	14944;14945;14946	chr2:178636233;178636232;178636231	chr2:179500960;179500959;179500958
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: Ig-88
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.2051
• 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	0.994	N	0.475	0.288	0.388174495139	gnomAD-4.0.0	1.72771E-06	None	None	None	None	N	None	0	0	None	5.38329E-05	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	0.7164	likely_pathogenic	0.7103	pathogenic	-0.769	Destabilizing	0.997	D	0.431	neutral	N	0.341573703	None	None	N
V/C	0.9519	likely_pathogenic	0.9467	pathogenic	-0.873	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
V/D	0.9614	likely_pathogenic	0.958	pathogenic	-0.643	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
V/E	0.9101	likely_pathogenic	0.9046	pathogenic	-0.676	Destabilizing	0.999	D	0.707	prob.delet.	N	0.40696698	None	None	N
V/F	0.7247	likely_pathogenic	0.6734	pathogenic	-0.644	Destabilizing	0.999	D	0.701	prob.delet.	None	None	None	None	N
V/G	0.8596	likely_pathogenic	0.8474	pathogenic	-0.987	Destabilizing	0.999	D	0.689	prob.delet.	N	0.40839799	None	None	N
V/H	0.9874	likely_pathogenic	0.9852	pathogenic	-0.365	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
V/I	0.108	likely_benign	0.1102	benign	-0.296	Destabilizing	0.995	D	0.496	neutral	None	None	None	None	N
V/K	0.9734	likely_pathogenic	0.9717	pathogenic	-0.771	Destabilizing	0.999	D	0.704	prob.delet.	None	None	None	None	N
V/L	0.5204	ambiguous	0.5262	ambiguous	-0.296	Destabilizing	0.994	D	0.475	neutral	N	0.323178924	None	None	N
V/M	0.5667	likely_pathogenic	0.5455	ambiguous	-0.575	Destabilizing	0.999	D	0.703	prob.delet.	N	0.40839799	None	None	N
V/N	0.9246	likely_pathogenic	0.9196	pathogenic	-0.629	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
V/P	0.8289	likely_pathogenic	0.8315	pathogenic	-0.42	Destabilizing	0.999	D	0.733	deleterious	None	None	None	None	N
V/Q	0.9487	likely_pathogenic	0.9422	pathogenic	-0.769	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
V/R	0.9585	likely_pathogenic	0.954	pathogenic	-0.296	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
V/S	0.8471	likely_pathogenic	0.8347	pathogenic	-1.038	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
V/T	0.7247	likely_pathogenic	0.717	pathogenic	-0.956	Destabilizing	0.998	D	0.627	neutral	None	None	None	None	N
V/W	0.9912	likely_pathogenic	0.9894	pathogenic	-0.755	Destabilizing	1.0	D	0.703	prob.delet.	None	None	None	None	N
V/Y	0.9652	likely_pathogenic	0.956	pathogenic	-0.47	Destabilizing	0.999	D	0.743	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.