TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30333	91222;91223;91224	chr2:178551903;178551902;178551901	chr2:179416630;179416629;179416628
N2AB	28692	86299;86300;86301	chr2:178551903;178551902;178551901	chr2:179416630;179416629;179416628
N2A	27765	83518;83519;83520	chr2:178551903;178551902;178551901	chr2:179416630;179416629;179416628
N2B	21268	64027;64028;64029	chr2:178551903;178551902;178551901	chr2:179416630;179416629;179416628
Novex-1	21393	64402;64403;64404	chr2:178551903;178551902;178551901	chr2:179416630;179416629;179416628
Novex-2	21460	64603;64604;64605	chr2:178551903;178551902;178551901	chr2:179416630;179416629;179416628
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-109
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.1722
• 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
I/M	None	None	0.171	N	0.537	0.157	0.512192450023	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
I/T	rs755369653	None	None	N	0.292	0.142	0.594537789615	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs755369653	None	None	N	0.292	0.142	0.594537789615	gnomAD-4.0.0	1.6112E-05	None	None	None	None	I	None	1.33486E-05	0	None	0	0	None	0	0	2.11905E-05	0	0
I/V	None	None	None	N	0.123	0.047	0.273503213844	gnomAD-4.0.0	3.18249E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85843E-06	1.43279E-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
I/A	0.315	likely_benign	0.3327	benign	-2.072	Highly Destabilizing	None	N	0.328	neutral	None	None	None	None	I
I/C	0.6365	likely_pathogenic	0.6164	pathogenic	-1.256	Destabilizing	0.356	N	0.591	neutral	None	None	None	None	I
I/D	0.9407	likely_pathogenic	0.9317	pathogenic	-1.772	Destabilizing	0.072	N	0.675	neutral	None	None	None	None	I
I/E	0.9033	likely_pathogenic	0.8912	pathogenic	-1.584	Destabilizing	0.072	N	0.619	neutral	None	None	None	None	I
I/F	0.4145	ambiguous	0.3909	ambiguous	-1.123	Destabilizing	0.072	N	0.561	neutral	None	None	None	None	I
I/G	0.7444	likely_pathogenic	0.7447	pathogenic	-2.585	Highly Destabilizing	0.031	N	0.485	neutral	None	None	None	None	I
I/H	0.8754	likely_pathogenic	0.8632	pathogenic	-1.964	Destabilizing	0.628	D	0.671	neutral	None	None	None	None	I
I/K	0.8663	likely_pathogenic	0.8604	pathogenic	-1.399	Destabilizing	0.055	N	0.625	neutral	N	0.503123977	None	None	I
I/L	0.1588	likely_benign	0.1462	benign	-0.625	Destabilizing	0.002	N	0.379	neutral	N	0.485041019	None	None	I
I/M	0.1895	likely_benign	0.189	benign	-0.554	Destabilizing	0.171	N	0.537	neutral	N	0.479739803	None	None	I
I/N	0.5546	ambiguous	0.5571	ambiguous	-1.573	Destabilizing	0.214	N	0.709	prob.delet.	None	None	None	None	I
I/P	0.5999	likely_pathogenic	0.5452	ambiguous	-1.083	Destabilizing	0.136	N	0.685	prob.neutral	None	None	None	None	I
I/Q	0.8302	likely_pathogenic	0.8155	pathogenic	-1.472	Destabilizing	0.356	N	0.709	prob.delet.	None	None	None	None	I
I/R	0.8027	likely_pathogenic	0.7888	pathogenic	-1.156	Destabilizing	0.171	N	0.715	prob.delet.	N	0.514480283	None	None	I
I/S	0.4222	ambiguous	0.4435	ambiguous	-2.328	Highly Destabilizing	0.016	N	0.441	neutral	None	None	None	None	I
I/T	0.2139	likely_benign	0.2535	benign	-1.996	Destabilizing	None	N	0.292	neutral	N	0.4747266	None	None	I
I/V	0.0577	likely_benign	0.0597	benign	-1.083	Destabilizing	None	N	0.123	neutral	N	0.40686545	None	None	I
I/W	0.9548	likely_pathogenic	0.9482	pathogenic	-1.435	Destabilizing	0.864	D	0.682	prob.neutral	None	None	None	None	I
I/Y	0.8252	likely_pathogenic	0.8028	pathogenic	-1.121	Destabilizing	0.356	N	0.645	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.