TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15520	46783;46784;46785	chr2:178619759;178619758;178619757	chr2:179484486;179484485;179484484
N2AB	13879	41860;41861;41862	chr2:178619759;178619758;178619757	chr2:179484486;179484485;179484484
N2A	12952	39079;39080;39081	chr2:178619759;178619758;178619757	chr2:179484486;179484485;179484484
N2B	6455	19588;19589;19590	chr2:178619759;178619758;178619757	chr2:179484486;179484485;179484484
Novex-1	6580	19963;19964;19965	chr2:178619759;178619758;178619757	chr2:179484486;179484485;179484484
Novex-2	6647	20164;20165;20166	chr2:178619759;178619758;178619757	chr2:179484486;179484485;179484484
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: Ig-107
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.6659
• 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/F	rs2057990397	None	0.993	N	0.681	0.245	0.775140819604	gnomAD-4.0.0	1.59391E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43377E-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	0.3916	ambiguous	0.3944	ambiguous	-0.347	Destabilizing	0.977	D	0.477	neutral	N	0.494264871	None	None	N
V/C	0.8476	likely_pathogenic	0.8902	pathogenic	-0.433	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
V/D	0.7521	likely_pathogenic	0.7104	pathogenic	-0.627	Destabilizing	0.999	D	0.681	prob.neutral	N	0.508486854	None	None	N
V/E	0.5626	ambiguous	0.5366	ambiguous	-0.736	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
V/F	0.2591	likely_benign	0.2379	benign	-0.669	Destabilizing	0.993	D	0.681	prob.neutral	N	0.505038171	None	None	N
V/G	0.4383	ambiguous	0.4474	ambiguous	-0.458	Destabilizing	0.999	D	0.681	prob.neutral	N	0.509150031	None	None	N
V/H	0.7529	likely_pathogenic	0.7498	pathogenic	-0.129	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
V/I	0.0911	likely_benign	0.096	benign	-0.194	Destabilizing	0.117	N	0.275	neutral	N	0.497287217	None	None	N
V/K	0.4795	ambiguous	0.5243	ambiguous	-0.431	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
V/L	0.2661	likely_benign	0.2707	benign	-0.194	Destabilizing	0.898	D	0.431	neutral	N	0.482348844	None	None	N
V/M	0.2301	likely_benign	0.2497	benign	-0.376	Destabilizing	0.995	D	0.623	neutral	None	None	None	None	N
V/N	0.5164	ambiguous	0.5304	ambiguous	-0.11	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
V/P	0.6005	likely_pathogenic	0.5877	pathogenic	-0.213	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
V/Q	0.4605	ambiguous	0.4713	ambiguous	-0.353	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
V/R	0.445	ambiguous	0.4502	ambiguous	0.056	Stabilizing	0.999	D	0.675	neutral	None	None	None	None	N
V/S	0.433	ambiguous	0.4326	ambiguous	-0.346	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	N
V/T	0.347	ambiguous	0.3621	ambiguous	-0.366	Destabilizing	0.983	D	0.597	neutral	None	None	None	None	N
V/W	0.9019	likely_pathogenic	0.9049	pathogenic	-0.785	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
V/Y	0.7227	likely_pathogenic	0.7276	pathogenic	-0.478	Destabilizing	0.999	D	0.677	prob.neutral	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.