TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5754	17485;17486;17487	chr2:178731506;178731505;178731504	chr2:179596233;179596232;179596231
N2AB	5437	16534;16535;16536	chr2:178731506;178731505;178731504	chr2:179596233;179596232;179596231
N2A	4510	13753;13754;13755	chr2:178731506;178731505;178731504	chr2:179596233;179596232;179596231
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-41
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4503
• 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/N	rs890346105	None	0.968	N	0.499	0.216	0.180583059064	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.93199E-04	None	0	0	0	0	0
K/N	rs890346105	None	0.968	N	0.499	0.216	0.180583059064	gnomAD-4.0.0	6.5672E-06	None	None	None	None	I	None	0	0	None	0	1.93648E-04	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
K/A	0.3471	ambiguous	0.313	benign	-0.025	Destabilizing	0.702	D	0.542	neutral	None	None	None	None	I
K/C	0.7252	likely_pathogenic	0.6674	pathogenic	-0.326	Destabilizing	0.999	D	0.616	neutral	None	None	None	None	I
K/D	0.6148	likely_pathogenic	0.5737	pathogenic	0.273	Stabilizing	0.976	D	0.523	neutral	None	None	None	None	I
K/E	0.1561	likely_benign	0.1455	benign	0.298	Stabilizing	0.896	D	0.521	neutral	N	0.444899055	None	None	I
K/F	0.7676	likely_pathogenic	0.7352	pathogenic	-0.171	Destabilizing	0.988	D	0.605	neutral	None	None	None	None	I
K/G	0.5359	ambiguous	0.4945	ambiguous	-0.24	Destabilizing	0.919	D	0.529	neutral	None	None	None	None	I
K/H	0.2884	likely_benign	0.27	benign	-0.421	Destabilizing	0.997	D	0.568	neutral	None	None	None	None	I
K/I	0.3825	ambiguous	0.3574	ambiguous	0.465	Stabilizing	0.261	N	0.385	neutral	None	None	None	None	I
K/L	0.3897	ambiguous	0.3656	ambiguous	0.465	Stabilizing	0.851	D	0.516	neutral	None	None	None	None	I
K/M	0.2573	likely_benign	0.2389	benign	0.17	Stabilizing	0.996	D	0.571	neutral	N	0.499672889	None	None	I
K/N	0.4338	ambiguous	0.3968	ambiguous	0.172	Stabilizing	0.968	D	0.499	neutral	N	0.513588349	None	None	I
K/P	0.9565	likely_pathogenic	0.9484	pathogenic	0.33	Stabilizing	0.996	D	0.581	neutral	None	None	None	None	I
K/Q	0.114	likely_benign	0.1103	benign	0.037	Stabilizing	0.968	D	0.551	neutral	N	0.502024561	None	None	I
K/R	0.0816	likely_benign	0.0792	benign	0.01	Stabilizing	0.059	N	0.151	neutral	N	0.499330973	None	None	I
K/S	0.3777	ambiguous	0.3371	benign	-0.378	Destabilizing	0.307	N	0.176	neutral	None	None	None	None	I
K/T	0.1664	likely_benign	0.1495	benign	-0.191	Destabilizing	0.896	D	0.54	neutral	N	0.473509808	None	None	I
K/V	0.3602	ambiguous	0.3329	benign	0.33	Stabilizing	0.851	D	0.517	neutral	None	None	None	None	I
K/W	0.7719	likely_pathogenic	0.7431	pathogenic	-0.167	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	I
K/Y	0.6432	likely_pathogenic	0.6142	pathogenic	0.189	Stabilizing	0.996	D	0.597	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.