TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6062	18409;18410;18411	chr2:178730216;178730215;178730214	chr2:179594943;179594942;179594941
N2AB	5745	17458;17459;17460	chr2:178730216;178730215;178730214	chr2:179594943;179594942;179594941
N2A	4818	14677;14678;14679	chr2:178730216;178730215;178730214	chr2:179594943;179594942;179594941
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-44
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.4111
• 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/N	rs56050216	None	0.968	N	0.657	0.236	0.184867976434	gnomAD-4.0.0	1.592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-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	0.4801	ambiguous	0.5609	ambiguous	-0.684	Destabilizing	0.919	D	0.618	neutral	None	None	None	None	N
K/C	0.8408	likely_pathogenic	0.8601	pathogenic	-0.541	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
K/D	0.7128	likely_pathogenic	0.7891	pathogenic	0.206	Stabilizing	0.988	D	0.721	prob.delet.	None	None	None	None	N
K/E	0.2106	likely_benign	0.2847	benign	0.327	Stabilizing	0.896	D	0.582	neutral	N	0.500349693	None	None	N
K/F	0.8282	likely_pathogenic	0.8672	pathogenic	-0.349	Destabilizing	0.076	N	0.515	neutral	None	None	None	None	N
K/G	0.6153	likely_pathogenic	0.6833	pathogenic	-1.04	Destabilizing	0.959	D	0.749	deleterious	None	None	None	None	N
K/H	0.4036	ambiguous	0.4467	ambiguous	-1.218	Destabilizing	0.997	D	0.718	prob.delet.	None	None	None	None	N
K/I	0.4424	ambiguous	0.5256	ambiguous	0.238	Stabilizing	0.952	D	0.764	deleterious	None	None	None	None	N
K/L	0.4436	ambiguous	0.5135	ambiguous	0.238	Stabilizing	0.662	D	0.672	neutral	None	None	None	None	N
K/M	0.2688	likely_benign	0.3226	benign	0.04	Stabilizing	0.64	D	0.513	neutral	N	0.49051863	None	None	N
K/N	0.477	ambiguous	0.5652	pathogenic	-0.325	Destabilizing	0.968	D	0.657	neutral	N	0.508334458	None	None	N
K/P	0.9059	likely_pathogenic	0.9227	pathogenic	-0.04	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
K/Q	0.1493	likely_benign	0.1828	benign	-0.343	Destabilizing	0.968	D	0.669	neutral	N	0.509931968	None	None	N
K/R	0.1015	likely_benign	0.1049	benign	-0.42	Destabilizing	0.059	N	0.303	neutral	N	0.489095336	None	None	N
K/S	0.4995	ambiguous	0.5969	pathogenic	-1.036	Destabilizing	0.919	D	0.611	neutral	None	None	None	None	N
K/T	0.2435	likely_benign	0.2906	benign	-0.702	Destabilizing	0.896	D	0.699	prob.neutral	N	0.517916733	None	None	N
K/V	0.4259	ambiguous	0.501	ambiguous	-0.04	Destabilizing	0.851	D	0.731	prob.delet.	None	None	None	None	N
K/W	0.803	likely_pathogenic	0.8324	pathogenic	-0.209	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
K/Y	0.692	likely_pathogenic	0.7405	pathogenic	0.057	Stabilizing	0.952	D	0.785	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.