TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27880	83863;83864;83865	chr2:178562494;178562493;178562492	chr2:179427221;179427220;179427219
N2AB	26239	78940;78941;78942	chr2:178562494;178562493;178562492	chr2:179427221;179427220;179427219
N2A	25312	76159;76160;76161	chr2:178562494;178562493;178562492	chr2:179427221;179427220;179427219
N2B	18815	56668;56669;56670	chr2:178562494;178562493;178562492	chr2:179427221;179427220;179427219
Novex-1	18940	57043;57044;57045	chr2:178562494;178562493;178562492	chr2:179427221;179427220;179427219
Novex-2	19007	57244;57245;57246	chr2:178562494;178562493;178562492	chr2:179427221;179427220;179427219
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-91
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1452
• 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
A/T	rs1319675982	-1.668	0.978	N	0.637	0.263	0.388970301349	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
A/T	rs1319675982	-1.668	0.978	N	0.637	0.263	0.388970301349	gnomAD-4.0.0	1.369E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.32369E-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
A/C	0.5939	likely_pathogenic	0.62	pathogenic	-1.834	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
A/D	0.9916	likely_pathogenic	0.9938	pathogenic	-2.382	Highly Destabilizing	0.999	D	0.792	deleterious	N	0.510530263	None	None	N
A/E	0.9787	likely_pathogenic	0.9844	pathogenic	-2.15	Highly Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
A/F	0.899	likely_pathogenic	0.9222	pathogenic	-0.804	Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
A/G	0.497	ambiguous	0.4998	ambiguous	-1.62	Destabilizing	0.996	D	0.627	neutral	N	0.4751939	None	None	N
A/H	0.9892	likely_pathogenic	0.9923	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
A/I	0.3756	ambiguous	0.4298	ambiguous	0.294	Stabilizing	0.967	D	0.662	neutral	None	None	None	None	N
A/K	0.9921	likely_pathogenic	0.9948	pathogenic	-1.179	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
A/L	0.4678	ambiguous	0.5155	ambiguous	0.294	Stabilizing	0.923	D	0.633	neutral	None	None	None	None	N
A/M	0.5609	ambiguous	0.6227	pathogenic	-0.339	Destabilizing	0.998	D	0.766	deleterious	None	None	None	None	N
A/N	0.967	likely_pathogenic	0.9746	pathogenic	-1.65	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
A/P	0.9815	likely_pathogenic	0.9867	pathogenic	-0.129	Destabilizing	0.999	D	0.789	deleterious	N	0.510276774	None	None	N
A/Q	0.9685	likely_pathogenic	0.9767	pathogenic	-1.391	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
A/R	0.9798	likely_pathogenic	0.9859	pathogenic	-1.399	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
A/S	0.3062	likely_benign	0.3287	benign	-2.13	Highly Destabilizing	0.989	D	0.625	neutral	N	0.487310674	None	None	N
A/T	0.2077	likely_benign	0.2304	benign	-1.742	Destabilizing	0.978	D	0.637	neutral	N	0.486803695	None	None	N
A/V	0.1373	likely_benign	0.1616	benign	-0.129	Destabilizing	0.198	N	0.318	neutral	N	0.369848644	None	None	N
A/W	0.9936	likely_pathogenic	0.9956	pathogenic	-1.512	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
A/Y	0.9727	likely_pathogenic	0.9803	pathogenic	-0.953	Destabilizing	0.999	D	0.776	deleterious	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.