TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20497	61714;61715;61716	chr2:178590236;178590235;178590234	chr2:179454963;179454962;179454961
N2AB	18856	56791;56792;56793	chr2:178590236;178590235;178590234	chr2:179454963;179454962;179454961
N2A	17929	54010;54011;54012	chr2:178590236;178590235;178590234	chr2:179454963;179454962;179454961
N2B	11432	34519;34520;34521	chr2:178590236;178590235;178590234	chr2:179454963;179454962;179454961
Novex-1	11557	34894;34895;34896	chr2:178590236;178590235;178590234	chr2:179454963;179454962;179454961
Novex-2	11624	35095;35096;35097	chr2:178590236;178590235;178590234	chr2:179454963;179454962;179454961
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-121
• Domain position: 19
• Structural Position: 31
• Q(SASA): 0.1694
• 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
L/P	None	None	0.523	N	0.66	0.315	0.739242410713	gnomAD-4.0.0	2.08202E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81538E-06	1.21966E-05	0
L/V	rs1323115557	-1.481	0.003	N	0.226	0.113	0.649506424125	gnomAD-2.1.1	4.36E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.5E-06	0
L/V	rs1323115557	-1.481	0.003	N	0.226	0.113	0.649506424125	gnomAD-4.0.0	1.64792E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94726E-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
L/A	0.1414	likely_benign	0.186	benign	-1.785	Destabilizing	0.001	N	0.377	neutral	None	None	None	None	N
L/C	0.4003	ambiguous	0.4545	ambiguous	-0.93	Destabilizing	0.836	D	0.593	neutral	None	None	None	None	N
L/D	0.5971	likely_pathogenic	0.6679	pathogenic	-1.355	Destabilizing	0.418	N	0.607	neutral	None	None	None	None	N
L/E	0.362	ambiguous	0.4143	ambiguous	-1.366	Destabilizing	0.418	N	0.599	neutral	None	None	None	None	N
L/F	0.1276	likely_benign	0.1577	benign	-1.298	Destabilizing	0.593	D	0.575	neutral	None	None	None	None	N
L/G	0.3778	ambiguous	0.4528	ambiguous	-2.104	Highly Destabilizing	0.129	N	0.563	neutral	None	None	None	None	N
L/H	0.1991	likely_benign	0.2385	benign	-1.324	Destabilizing	0.94	D	0.608	neutral	None	None	None	None	N
L/I	0.089	likely_benign	0.1074	benign	-0.979	Destabilizing	0.003	N	0.208	neutral	N	0.445016485	None	None	N
L/K	0.3039	likely_benign	0.3355	benign	-1.224	Destabilizing	0.418	N	0.582	neutral	None	None	None	None	N
L/M	0.1027	likely_benign	0.1212	benign	-0.658	Destabilizing	0.836	D	0.573	neutral	None	None	None	None	N
L/N	0.2581	likely_benign	0.3175	benign	-0.954	Destabilizing	0.418	N	0.637	neutral	None	None	None	None	N
L/P	0.305	likely_benign	0.3927	ambiguous	-1.217	Destabilizing	0.523	D	0.66	neutral	N	0.422139625	None	None	N
L/Q	0.1583	likely_benign	0.1942	benign	-1.179	Destabilizing	0.794	D	0.653	neutral	N	0.431161753	None	None	N
L/R	0.2465	likely_benign	0.269	benign	-0.567	Destabilizing	0.655	D	0.654	neutral	N	0.427641446	None	None	N
L/S	0.1626	likely_benign	0.2288	benign	-1.535	Destabilizing	0.004	N	0.447	neutral	None	None	None	None	N
L/T	0.1203	likely_benign	0.1597	benign	-1.438	Destabilizing	0.004	N	0.373	neutral	None	None	None	None	N
L/V	0.0839	likely_benign	0.1003	benign	-1.217	Destabilizing	0.003	N	0.226	neutral	N	0.420158113	None	None	N
L/W	0.2786	likely_benign	0.3184	benign	-1.356	Destabilizing	0.983	D	0.619	neutral	None	None	None	None	N
L/Y	0.3145	likely_benign	0.3612	ambiguous	-1.167	Destabilizing	0.94	D	0.629	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.