TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27288	82087;82088;82089	chr2:178564270;178564269;178564268	chr2:179428997;179428996;179428995
N2AB	25647	77164;77165;77166	chr2:178564270;178564269;178564268	chr2:179428997;179428996;179428995
N2A	24720	74383;74384;74385	chr2:178564270;178564269;178564268	chr2:179428997;179428996;179428995
N2B	18223	54892;54893;54894	chr2:178564270;178564269;178564268	chr2:179428997;179428996;179428995
Novex-1	18348	55267;55268;55269	chr2:178564270;178564269;178564268	chr2:179428997;179428996;179428995
Novex-2	18415	55468;55469;55470	chr2:178564270;178564269;178564268	chr2:179428997;179428996;179428995
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-140
• Domain position: 11
• Structural Position: 18
• Q(SASA): 0.7673
• 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
H/R	None	None	None	N	0.15	0.129	0.183819452728	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
H/A	0.244	likely_benign	0.2465	benign	0.05	Stabilizing	0.055	N	0.398	neutral	None	None	None	None	I
H/C	0.15	likely_benign	0.1482	benign	0.512	Stabilizing	0.958	D	0.467	neutral	None	None	None	None	I
H/D	0.2715	likely_benign	0.267	benign	-0.232	Destabilizing	0.042	N	0.401	neutral	N	0.455654766	None	None	I
H/E	0.3053	likely_benign	0.2988	benign	-0.19	Destabilizing	0.055	N	0.239	neutral	None	None	None	None	I
H/F	0.31	likely_benign	0.3073	benign	0.903	Stabilizing	0.667	D	0.467	neutral	None	None	None	None	I
H/G	0.2737	likely_benign	0.2722	benign	-0.251	Destabilizing	0.055	N	0.409	neutral	None	None	None	None	I
H/I	0.3588	ambiguous	0.355	ambiguous	0.834	Stabilizing	0.667	D	0.503	neutral	None	None	None	None	I
H/K	0.1676	likely_benign	0.1564	benign	-0.054	Destabilizing	0.002	N	0.223	neutral	None	None	None	None	I
H/L	0.1118	likely_benign	0.1086	benign	0.834	Stabilizing	0.081	N	0.441	neutral	N	0.441917465	None	None	I
H/M	0.3858	ambiguous	0.3937	ambiguous	0.576	Stabilizing	0.859	D	0.488	neutral	None	None	None	None	I
H/N	0.0984	likely_benign	0.0968	benign	-0.138	Destabilizing	None	N	0.146	neutral	N	0.400628203	None	None	I
H/P	0.1502	likely_benign	0.1362	benign	0.597	Stabilizing	0.301	N	0.502	neutral	N	0.454462688	None	None	I
H/Q	0.1447	likely_benign	0.1399	benign	0.008	Stabilizing	0.175	N	0.297	neutral	N	0.418077813	None	None	I
H/R	0.0737	likely_benign	0.0697	benign	-0.643	Destabilizing	None	N	0.15	neutral	N	0.41105584	None	None	I
H/S	0.2136	likely_benign	0.2126	benign	-0.021	Destabilizing	0.005	N	0.221	neutral	None	None	None	None	I
H/T	0.2513	likely_benign	0.2472	benign	0.122	Stabilizing	0.055	N	0.451	neutral	None	None	None	None	I
H/V	0.2685	likely_benign	0.274	benign	0.597	Stabilizing	0.22	N	0.487	neutral	None	None	None	None	I
H/W	0.3606	ambiguous	0.348	ambiguous	0.967	Stabilizing	0.958	D	0.485	neutral	None	None	None	None	I
H/Y	0.1059	likely_benign	0.105	benign	1.162	Stabilizing	0.301	N	0.379	neutral	N	0.492250285	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.