TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20521	61786;61787;61788	chr2:178590164;178590163;178590162	chr2:179454891;179454890;179454889
N2AB	18880	56863;56864;56865	chr2:178590164;178590163;178590162	chr2:179454891;179454890;179454889
N2A	17953	54082;54083;54084	chr2:178590164;178590163;178590162	chr2:179454891;179454890;179454889
N2B	11456	34591;34592;34593	chr2:178590164;178590163;178590162	chr2:179454891;179454890;179454889
Novex-1	11581	34966;34967;34968	chr2:178590164;178590163;178590162	chr2:179454891;179454890;179454889
Novex-2	11648	35167;35168;35169	chr2:178590164;178590163;178590162	chr2:179454891;179454890;179454889
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-121
• Domain position: 43
• Structural Position: 109
• Q(SASA): 0.8304
• 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
K/E	rs2049901780	None	0.885	N	0.471	0.159	0.206339911435	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs2049901780	None	0.885	N	0.471	0.159	0.206339911435	gnomAD-4.0.0	6.57652E-06	None	None	None	None	I	None	2.41336E-05	0	None	0	0	None	0	0	0	0	0
K/N	None	None	0.1	N	0.321	0.076	0.115124310173	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.2871	likely_benign	0.2944	benign	-0.037	Destabilizing	0.953	D	0.439	neutral	None	None	None	None	I
K/C	0.7193	likely_pathogenic	0.7207	pathogenic	-0.549	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	I
K/D	0.3392	likely_benign	0.3458	ambiguous	-0.415	Destabilizing	0.91	D	0.422	neutral	None	None	None	None	I
K/E	0.1538	likely_benign	0.1603	benign	-0.434	Destabilizing	0.885	D	0.471	neutral	N	0.44783692	None	None	I
K/F	0.8273	likely_pathogenic	0.8394	pathogenic	-0.42	Destabilizing	0.998	D	0.553	neutral	None	None	None	None	I
K/G	0.3048	likely_benign	0.3273	benign	-0.137	Destabilizing	0.91	D	0.433	neutral	None	None	None	None	I
K/H	0.334	likely_benign	0.3431	ambiguous	-0.188	Destabilizing	0.993	D	0.455	neutral	None	None	None	None	I
K/I	0.4533	ambiguous	0.472	ambiguous	0.145	Stabilizing	0.993	D	0.563	neutral	None	None	None	None	I
K/L	0.399	ambiguous	0.4243	ambiguous	0.145	Stabilizing	0.986	D	0.419	neutral	None	None	None	None	I
K/M	0.2932	likely_benign	0.3044	benign	-0.23	Destabilizing	0.998	D	0.446	neutral	N	0.463605379	None	None	I
K/N	0.2544	likely_benign	0.2648	benign	-0.089	Destabilizing	0.1	N	0.321	neutral	N	0.47184993	None	None	I
K/P	0.3543	ambiguous	0.3533	ambiguous	0.105	Stabilizing	0.993	D	0.449	neutral	None	None	None	None	I
K/Q	0.1361	likely_benign	0.1389	benign	-0.225	Destabilizing	0.322	N	0.309	neutral	N	0.493745355	None	None	I
K/R	0.1034	likely_benign	0.1026	benign	-0.17	Destabilizing	0.885	D	0.441	neutral	N	0.438084073	None	None	I
K/S	0.2973	likely_benign	0.3029	benign	-0.418	Destabilizing	0.91	D	0.437	neutral	None	None	None	None	I
K/T	0.1765	likely_benign	0.1842	benign	-0.335	Destabilizing	0.939	D	0.425	neutral	N	0.471119211	None	None	I
K/V	0.4031	ambiguous	0.4142	ambiguous	0.105	Stabilizing	0.993	D	0.467	neutral	None	None	None	None	I
K/W	0.8068	likely_pathogenic	0.8061	pathogenic	-0.542	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	I
K/Y	0.65	likely_pathogenic	0.6683	pathogenic	-0.2	Destabilizing	0.998	D	0.503	neutral	None	None	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.