TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3999	12220;12221;12222	chr2:178741238;178741237;178741236	chr2:179605965;179605964;179605963
N2AB	3682	11269;11270;11271	chr2:178741238;178741237;178741236	chr2:179605965;179605964;179605963
N2A	None	None	chr2:None	chr2:None
N2B	3636	11131;11132;11133	chr2:178741238;178741237;178741236	chr2:179605965;179605964;179605963
Novex-1	3761	11506;11507;11508	chr2:178741238;178741237;178741236	chr2:179605965;179605964;179605963
Novex-2	3828	11707;11708;11709	chr2:178741238;178741237;178741236	chr2:179605965;179605964;179605963
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-28
• Domain position: 62
• Structural Position: 141
• Q(SASA): 0.5248
• 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
N/S	rs199844346	-0.404	0.023	N	0.105	0.067	None	gnomAD-2.1.1	1.39462E-04	None	None	None	None	I	None	0	1.41499E-04	None	3.87072E-04	0	None	0	None	0	2.34716E-04	0
N/S	rs199844346	-0.404	0.023	N	0.105	0.067	None	gnomAD-3.1.2	9.86E-05	None	None	None	None	I	None	0	2.61883E-04	0	2.88184E-04	0	None	0	0	1.32322E-04	0	4.78011E-04
N/S	rs199844346	-0.404	0.023	N	0.105	0.067	None	gnomAD-4.0.0	7.8086E-05	None	None	None	None	I	None	0	1.83315E-04	None	4.39189E-04	0	None	0	1.15512E-03	6.7807E-05	0	2.40085E-04

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
N/A	0.5661	likely_pathogenic	0.5373	ambiguous	-0.744	Destabilizing	0.329	N	0.378	neutral	None	None	None	None	I
N/C	0.5045	ambiguous	0.4838	ambiguous	0.015	Stabilizing	0.995	D	0.425	neutral	None	None	None	None	I
N/D	0.4814	ambiguous	0.4692	ambiguous	-0.817	Destabilizing	0.425	N	0.227	neutral	N	0.485414526	None	None	I
N/E	0.7377	likely_pathogenic	0.7305	pathogenic	-0.7	Destabilizing	0.329	N	0.214	neutral	None	None	None	None	I
N/F	0.8275	likely_pathogenic	0.8082	pathogenic	-0.441	Destabilizing	0.944	D	0.441	neutral	None	None	None	None	I
N/G	0.6261	likely_pathogenic	0.5937	pathogenic	-1.105	Destabilizing	0.495	N	0.237	neutral	None	None	None	None	I
N/H	0.22	likely_benign	0.2277	benign	-0.941	Destabilizing	0.013	N	0.174	neutral	N	0.498357913	None	None	I
N/I	0.4816	ambiguous	0.4647	ambiguous	0.18	Stabilizing	0.927	D	0.443	neutral	N	0.51125321	None	None	I
N/K	0.5617	ambiguous	0.5999	pathogenic	-0.319	Destabilizing	0.023	N	0.101	neutral	N	0.481511927	None	None	I
N/L	0.4572	ambiguous	0.4481	ambiguous	0.18	Stabilizing	0.704	D	0.471	neutral	None	None	None	None	I
N/M	0.6142	likely_pathogenic	0.5939	pathogenic	0.608	Stabilizing	0.944	D	0.413	neutral	None	None	None	None	I
N/P	0.8541	likely_pathogenic	0.8568	pathogenic	-0.097	Destabilizing	0.828	D	0.442	neutral	None	None	None	None	I
N/Q	0.649	likely_pathogenic	0.6519	pathogenic	-0.898	Destabilizing	0.013	N	0.086	neutral	None	None	None	None	I
N/R	0.5632	ambiguous	0.5907	pathogenic	-0.45	Destabilizing	0.007	N	0.141	neutral	None	None	None	None	I
N/S	0.1535	likely_benign	0.1478	benign	-0.939	Destabilizing	0.023	N	0.105	neutral	N	0.469822092	None	None	I
N/T	0.3237	likely_benign	0.3164	benign	-0.635	Destabilizing	0.27	N	0.179	neutral	N	0.493384545	None	None	I
N/V	0.5318	ambiguous	0.5166	ambiguous	-0.097	Destabilizing	0.828	D	0.463	neutral	None	None	None	None	I
N/W	0.9148	likely_pathogenic	0.8994	pathogenic	-0.258	Destabilizing	0.995	D	0.453	neutral	None	None	None	None	I
N/Y	0.3288	likely_benign	0.3256	benign	-0.016	Destabilizing	0.863	D	0.429	neutral	N	0.50917363	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.