TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21950	66073;66074;66075	chr2:178582955;178582954;178582953	chr2:179447682;179447681;179447680
N2AB	20309	61150;61151;61152	chr2:178582955;178582954;178582953	chr2:179447682;179447681;179447680
N2A	19382	58369;58370;58371	chr2:178582955;178582954;178582953	chr2:179447682;179447681;179447680
N2B	12885	38878;38879;38880	chr2:178582955;178582954;178582953	chr2:179447682;179447681;179447680
Novex-1	13010	39253;39254;39255	chr2:178582955;178582954;178582953	chr2:179447682;179447681;179447680
Novex-2	13077	39454;39455;39456	chr2:178582955;178582954;178582953	chr2:179447682;179447681;179447680
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-125
• Domain position: 85
• Structural Position: 173
• Q(SASA): 0.5882
• 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
K/R	None	None	0.235	N	0.302	0.111	0.324161360171	gnomAD-4.0.0	1.81447E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.86588E-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
K/A	0.4754	ambiguous	0.436	ambiguous	-0.489	Destabilizing	0.983	D	0.621	neutral	None	None	None	None	N
K/C	0.6852	likely_pathogenic	0.6302	pathogenic	-0.533	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/D	0.8459	likely_pathogenic	0.8003	pathogenic	0.05	Stabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
K/E	0.4092	ambiguous	0.369	ambiguous	0.121	Stabilizing	0.977	D	0.565	neutral	N	0.457038846	None	None	N
K/F	0.8398	likely_pathogenic	0.8157	pathogenic	-0.391	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/G	0.6805	likely_pathogenic	0.6369	pathogenic	-0.806	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
K/H	0.28	likely_benign	0.2583	benign	-1.213	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
K/I	0.4828	ambiguous	0.4338	ambiguous	0.308	Stabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
K/L	0.4781	ambiguous	0.4418	ambiguous	0.308	Stabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	N
K/M	0.3088	likely_benign	0.2801	benign	0.268	Stabilizing	1.0	D	0.692	prob.neutral	N	0.504219504	None	None	N
K/N	0.5915	likely_pathogenic	0.5548	ambiguous	-0.215	Destabilizing	0.993	D	0.686	prob.neutral	N	0.470240217	None	None	N
K/P	0.7696	likely_pathogenic	0.7498	pathogenic	0.073	Stabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
K/Q	0.1389	likely_benign	0.1337	benign	-0.386	Destabilizing	0.993	D	0.69	prob.neutral	N	0.457406992	None	None	N
K/R	0.0931	likely_benign	0.0915	benign	-0.466	Destabilizing	0.235	N	0.302	neutral	N	0.468528063	None	None	N
K/S	0.5261	ambiguous	0.4952	ambiguous	-0.904	Destabilizing	0.983	D	0.625	neutral	None	None	None	None	N
K/T	0.2146	likely_benign	0.1932	benign	-0.64	Destabilizing	0.997	D	0.713	prob.delet.	N	0.456540201	None	None	N
K/V	0.4568	ambiguous	0.4182	ambiguous	0.073	Stabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	N
K/W	0.8333	likely_pathogenic	0.8091	pathogenic	-0.243	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
K/Y	0.7537	likely_pathogenic	0.7132	pathogenic	0.071	Stabilizing	0.999	D	0.734	prob.delet.	None	None	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.