TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17011	51256;51257;51258	chr2:178611098;178611097;178611096	chr2:179475825;179475824;179475823
N2AB	15370	46333;46334;46335	chr2:178611098;178611097;178611096	chr2:179475825;179475824;179475823
N2A	14443	43552;43553;43554	chr2:178611098;178611097;178611096	chr2:179475825;179475824;179475823
N2B	7946	24061;24062;24063	chr2:178611098;178611097;178611096	chr2:179475825;179475824;179475823
Novex-1	8071	24436;24437;24438	chr2:178611098;178611097;178611096	chr2:179475825;179475824;179475823
Novex-2	8138	24637;24638;24639	chr2:178611098;178611097;178611096	chr2:179475825;179475824;179475823
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-111
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.444
• 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/N	rs1471950857	-0.81	0.001	N	0.193	0.121	0.173771789658	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
H/N	rs1471950857	-0.81	0.001	N	0.193	0.121	0.173771789658	gnomAD-4.0.0	1.59326E-06	None	None	None	None	N	None	0	2.28833E-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
H/A	0.2397	likely_benign	0.2712	benign	-0.671	Destabilizing	0.129	N	0.396	neutral	None	None	None	None	N
H/C	0.137	likely_benign	0.1361	benign	-0.132	Destabilizing	0.983	D	0.521	neutral	None	None	None	None	N
H/D	0.2522	likely_benign	0.278	benign	-0.746	Destabilizing	0.101	N	0.383	neutral	N	0.502171233	None	None	N
H/E	0.2606	likely_benign	0.2798	benign	-0.664	Destabilizing	0.129	N	0.305	neutral	None	None	None	None	N
H/F	0.194	likely_benign	0.2123	benign	0.249	Stabilizing	0.557	D	0.591	neutral	None	None	None	None	N
H/G	0.3316	likely_benign	0.3608	ambiguous	-1.001	Destabilizing	0.129	N	0.412	neutral	None	None	None	None	N
H/I	0.1817	likely_benign	0.1973	benign	0.234	Stabilizing	0.264	N	0.47	neutral	None	None	None	None	N
H/K	0.2054	likely_benign	0.2287	benign	-0.623	Destabilizing	0.129	N	0.375	neutral	None	None	None	None	N
H/L	0.0975	likely_benign	0.1026	benign	0.234	Stabilizing	None	N	0.435	neutral	N	0.48408601	None	None	N
H/M	0.2951	likely_benign	0.3245	benign	0.081	Stabilizing	0.716	D	0.546	neutral	None	None	None	None	N
H/N	0.1006	likely_benign	0.1141	benign	-0.621	Destabilizing	0.001	N	0.193	neutral	N	0.495891894	None	None	N
H/P	0.6971	likely_pathogenic	0.7156	pathogenic	-0.048	Destabilizing	0.523	D	0.583	neutral	N	0.508350679	None	None	N
H/Q	0.1384	likely_benign	0.1531	benign	-0.388	Destabilizing	0.007	N	0.227	neutral	N	0.441841628	None	None	N
H/R	0.1009	likely_benign	0.1056	benign	-0.989	Destabilizing	0.213	N	0.322	neutral	N	0.480586693	None	None	N
H/S	0.1774	likely_benign	0.1975	benign	-0.654	Destabilizing	0.129	N	0.391	neutral	None	None	None	None	N
H/T	0.1737	likely_benign	0.2006	benign	-0.48	Destabilizing	0.004	N	0.358	neutral	None	None	None	None	N
H/V	0.1579	likely_benign	0.1697	benign	-0.048	Destabilizing	0.129	N	0.411	neutral	None	None	None	None	N
H/W	0.304	likely_benign	0.3006	benign	0.336	Stabilizing	0.983	D	0.555	neutral	None	None	None	None	N
H/Y	0.0856	likely_benign	0.0904	benign	0.576	Stabilizing	0.523	D	0.403	neutral	N	0.505557085	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.