TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8350	25273;25274;25275	chr2:178717958;178717957;178717956	chr2:179582685;179582684;179582683
N2AB	8033	24322;24323;24324	chr2:178717958;178717957;178717956	chr2:179582685;179582684;179582683
N2A	7106	21541;21542;21543	chr2:178717958;178717957;178717956	chr2:179582685;179582684;179582683
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-68
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.1905
• Predicted PPI site: I

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	rs915984764	None	0.174	N	0.251	0.208	0.439339381091	gnomAD-4.0.0	2.0553E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73853E-04	9.00722E-07	1.16071E-05	0
V/M	None	None	0.916	N	0.545	0.207	0.417586769301	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.92456E-04	None	0	0	0	0	0
V/M	None	None	0.916	N	0.545	0.207	0.417586769301	gnomAD-4.0.0	6.5722E-06	None	None	None	None	I	None	0	0	None	0	1.92456E-04	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	0.1679	likely_benign	0.1849	benign	-1.365	Destabilizing	0.174	N	0.251	neutral	N	0.416059015	None	None	I
V/C	0.7383	likely_pathogenic	0.7753	pathogenic	-0.894	Destabilizing	0.996	D	0.533	neutral	None	None	None	None	I
V/D	0.2554	likely_benign	0.2827	benign	-1.079	Destabilizing	0.023	N	0.398	neutral	None	None	None	None	I
V/E	0.1904	likely_benign	0.2051	benign	-1.085	Destabilizing	0.012	N	0.341	neutral	N	0.4228862	None	None	I
V/F	0.1172	likely_benign	0.1245	benign	-1.04	Destabilizing	0.953	D	0.573	neutral	None	None	None	None	I
V/G	0.225	likely_benign	0.2584	benign	-1.679	Destabilizing	0.763	D	0.569	neutral	D	0.530421884	None	None	I
V/H	0.3847	ambiguous	0.4095	ambiguous	-1.199	Destabilizing	0.989	D	0.587	neutral	None	None	None	None	I
V/I	0.0762	likely_benign	0.0773	benign	-0.61	Destabilizing	0.091	N	0.444	neutral	None	None	None	None	I
V/K	0.2047	likely_benign	0.2165	benign	-1.144	Destabilizing	0.729	D	0.575	neutral	None	None	None	None	I
V/L	0.1293	likely_benign	0.1368	benign	-0.61	Destabilizing	None	N	0.129	neutral	N	0.433644698	None	None	I
V/M	0.1106	likely_benign	0.1193	benign	-0.453	Destabilizing	0.916	D	0.545	neutral	N	0.463967605	None	None	I
V/N	0.1933	likely_benign	0.201	benign	-0.914	Destabilizing	0.286	N	0.599	neutral	None	None	None	None	I
V/P	0.5762	likely_pathogenic	0.6182	pathogenic	-0.826	Destabilizing	0.448	N	0.629	neutral	None	None	None	None	I
V/Q	0.2046	likely_benign	0.2137	benign	-1.08	Destabilizing	0.657	D	0.625	neutral	None	None	None	None	I
V/R	0.1901	likely_benign	0.208	benign	-0.624	Destabilizing	0.953	D	0.625	neutral	None	None	None	None	I
V/S	0.1675	likely_benign	0.1816	benign	-1.446	Destabilizing	0.048	N	0.317	neutral	None	None	None	None	I
V/T	0.146	likely_benign	0.1479	benign	-1.342	Destabilizing	0.016	N	0.151	neutral	None	None	None	None	I
V/W	0.6813	likely_pathogenic	0.7226	pathogenic	-1.226	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	I
V/Y	0.3928	ambiguous	0.4147	ambiguous	-0.934	Destabilizing	0.976	D	0.566	neutral	None	None	None	None	I

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.