TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14759	44500;44501;44502	chr2:178630247;178630246;178630245	chr2:179494974;179494973;179494972
N2AB	13118	39577;39578;39579	chr2:178630247;178630246;178630245	chr2:179494974;179494973;179494972
N2A	12191	36796;36797;36798	chr2:178630247;178630246;178630245	chr2:179494974;179494973;179494972
N2B	5694	17305;17306;17307	chr2:178630247;178630246;178630245	chr2:179494974;179494973;179494972
Novex-1	5819	17680;17681;17682	chr2:178630247;178630246;178630245	chr2:179494974;179494973;179494972
Novex-2	5886	17881;17882;17883	chr2:178630247;178630246;178630245	chr2:179494974;179494973;179494972
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: Ig-98
• Domain position: 85
• Structural Position: 176
• Q(SASA): 0.1223
• 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/D	None	None	0.999	D	0.849	0.641	0.756160954892	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.9315	likely_pathogenic	0.9555	pathogenic	-2.321	Highly Destabilizing	0.997	D	0.53	neutral	D	0.67817143	None	None	N
V/C	0.9805	likely_pathogenic	0.9853	pathogenic	-1.966	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/D	0.9957	likely_pathogenic	0.9978	pathogenic	-3.28	Highly Destabilizing	0.999	D	0.849	deleterious	D	0.68148407	None	None	N
V/E	0.9841	likely_pathogenic	0.9901	pathogenic	-3.139	Highly Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
V/F	0.9248	likely_pathogenic	0.9501	pathogenic	-1.334	Destabilizing	0.999	D	0.866	deleterious	D	0.681112696	None	None	N
V/G	0.899	likely_pathogenic	0.9337	pathogenic	-2.739	Highly Destabilizing	0.999	D	0.831	deleterious	D	0.68148407	None	None	N
V/H	0.9979	likely_pathogenic	0.9985	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/I	0.1466	likely_benign	0.15	benign	-1.165	Destabilizing	0.994	D	0.502	neutral	D	0.552690579	None	None	N
V/K	0.9885	likely_pathogenic	0.993	pathogenic	-2.01	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
V/L	0.8233	likely_pathogenic	0.8468	pathogenic	-1.165	Destabilizing	0.994	D	0.54	neutral	D	0.676411813	None	None	N
V/M	0.8576	likely_pathogenic	0.9074	pathogenic	-1.265	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
V/N	0.9865	likely_pathogenic	0.9917	pathogenic	-2.221	Highly Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
V/P	0.9887	likely_pathogenic	0.9915	pathogenic	-1.527	Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
V/Q	0.9881	likely_pathogenic	0.992	pathogenic	-2.196	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/R	0.9799	likely_pathogenic	0.9864	pathogenic	-1.609	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
V/S	0.9702	likely_pathogenic	0.9802	pathogenic	-2.687	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
V/T	0.9473	likely_pathogenic	0.9629	pathogenic	-2.444	Highly Destabilizing	0.998	D	0.603	neutral	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9989	pathogenic	-1.785	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
V/Y	0.9926	likely_pathogenic	0.9945	pathogenic	-1.554	Destabilizing	0.999	D	0.851	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.