TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16763	50512;50513;50514	chr2:178612124;178612123;178612122	chr2:179476851;179476850;179476849
N2AB	15122	45589;45590;45591	chr2:178612124;178612123;178612122	chr2:179476851;179476850;179476849
N2A	14195	42808;42809;42810	chr2:178612124;178612123;178612122	chr2:179476851;179476850;179476849
N2B	7698	23317;23318;23319	chr2:178612124;178612123;178612122	chr2:179476851;179476850;179476849
Novex-1	7823	23692;23693;23694	chr2:178612124;178612123;178612122	chr2:179476851;179476850;179476849
Novex-2	7890	23893;23894;23895	chr2:178612124;178612123;178612122	chr2:179476851;179476850;179476849
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: Fn3-10
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2087
• 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/M	rs927015538	-0.876	1.0	D	0.695	0.41	0.666881549798	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
V/M	rs927015538	-0.876	1.0	D	0.695	0.41	0.666881549798	gnomAD-4.0.0	3.1909E-06	None	None	None	None	N	None	0	4.58905E-05	None	0	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	0.5319	ambiguous	0.4619	ambiguous	-1.749	Destabilizing	0.999	D	0.533	neutral	N	0.478892311	None	None	N
V/C	0.8754	likely_pathogenic	0.8409	pathogenic	-1.448	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
V/D	0.9138	likely_pathogenic	0.8807	pathogenic	-2.652	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/E	0.7997	likely_pathogenic	0.7602	pathogenic	-2.587	Highly Destabilizing	1.0	D	0.82	deleterious	D	0.678021652	None	None	N
V/F	0.4751	ambiguous	0.4137	ambiguous	-1.301	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/G	0.7016	likely_pathogenic	0.63	pathogenic	-2.139	Highly Destabilizing	1.0	D	0.82	deleterious	D	0.619925979	None	None	N
V/H	0.9138	likely_pathogenic	0.8752	pathogenic	-1.948	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/I	0.0981	likely_benign	0.0903	benign	-0.726	Destabilizing	0.998	D	0.493	neutral	None	None	None	None	N
V/K	0.707	likely_pathogenic	0.6499	pathogenic	-1.563	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
V/L	0.4951	ambiguous	0.4546	ambiguous	-0.726	Destabilizing	0.997	D	0.521	neutral	N	0.474500919	None	None	N
V/M	0.3097	likely_benign	0.2614	benign	-0.616	Destabilizing	1.0	D	0.695	prob.neutral	D	0.589177341	None	None	N
V/N	0.8019	likely_pathogenic	0.7205	pathogenic	-1.588	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/P	0.9795	likely_pathogenic	0.977	pathogenic	-1.036	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/Q	0.7378	likely_pathogenic	0.6846	pathogenic	-1.677	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/R	0.6949	likely_pathogenic	0.6406	pathogenic	-1.17	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/S	0.681	likely_pathogenic	0.5938	pathogenic	-2.025	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/T	0.4372	ambiguous	0.3378	benign	-1.851	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
V/W	0.9715	likely_pathogenic	0.9622	pathogenic	-1.731	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/Y	0.8769	likely_pathogenic	0.8417	pathogenic	-1.399	Destabilizing	1.0	D	0.804	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.