TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14537	43834;43835;43836	chr2:178632285;178632284;178632283	chr2:179497012;179497011;179497010
N2AB	12896	38911;38912;38913	chr2:178632285;178632284;178632283	chr2:179497012;179497011;179497010
N2A	11969	36130;36131;36132	chr2:178632285;178632284;178632283	chr2:179497012;179497011;179497010
N2B	5472	16639;16640;16641	chr2:178632285;178632284;178632283	chr2:179497012;179497011;179497010
Novex-1	5597	17014;17015;17016	chr2:178632285;178632284;178632283	chr2:179497012;179497011;179497010
Novex-2	5664	17215;17216;17217	chr2:178632285;178632284;178632283	chr2:179497012;179497011;179497010
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-96
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.7472
• 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
H/Q	None	None	1.0	N	0.671	0.323	0.314716216878	gnomAD-4.0.0	6.85972E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00847E-07	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
H/A	0.5377	ambiguous	0.4099	ambiguous	0.459	Stabilizing	0.999	D	0.577	neutral	None	None	None	None	N
H/C	0.4199	ambiguous	0.3249	benign	0.726	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
H/D	0.3886	ambiguous	0.3019	benign	-0.209	Destabilizing	1.0	D	0.649	neutral	D	0.60998294	None	None	N
H/E	0.527	ambiguous	0.4035	ambiguous	-0.19	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
H/F	0.4477	ambiguous	0.3631	ambiguous	1.096	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
H/G	0.5262	ambiguous	0.4256	ambiguous	0.204	Stabilizing	0.999	D	0.592	neutral	None	None	None	None	N
H/I	0.5541	ambiguous	0.4242	ambiguous	1.103	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
H/K	0.4588	ambiguous	0.3487	ambiguous	0.356	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	N
H/L	0.2405	likely_benign	0.1872	benign	1.103	Stabilizing	1.0	D	0.665	neutral	D	0.52751297	None	None	N
H/M	0.6911	likely_pathogenic	0.5903	pathogenic	0.753	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	N
H/N	0.1901	likely_benign	0.1489	benign	0.239	Stabilizing	0.999	D	0.583	neutral	D	0.603712258	None	None	N
H/P	0.2221	likely_benign	0.1718	benign	0.913	Stabilizing	1.0	D	0.66	neutral	D	0.610535365	None	None	N
H/Q	0.3815	ambiguous	0.2649	benign	0.333	Stabilizing	1.0	D	0.671	neutral	N	0.506269682	None	None	N
H/R	0.2113	likely_benign	0.153	benign	-0.237	Destabilizing	1.0	D	0.645	neutral	D	0.537766802	None	None	N
H/S	0.3972	ambiguous	0.3033	benign	0.417	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	N
H/T	0.5503	ambiguous	0.4225	ambiguous	0.532	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
H/V	0.5015	ambiguous	0.3789	ambiguous	0.913	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
H/W	0.4997	ambiguous	0.4401	ambiguous	1.017	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
H/Y	0.1662	likely_benign	0.1337	benign	1.276	Stabilizing	0.999	D	0.539	neutral	D	0.545259186	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.