TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27192	81799;81800;81801	chr2:178564558;178564557;178564556	chr2:179429285;179429284;179429283
N2AB	25551	76876;76877;76878	chr2:178564558;178564557;178564556	chr2:179429285;179429284;179429283
N2A	24624	74095;74096;74097	chr2:178564558;178564557;178564556	chr2:179429285;179429284;179429283
N2B	18127	54604;54605;54606	chr2:178564558;178564557;178564556	chr2:179429285;179429284;179429283
Novex-1	18252	54979;54980;54981	chr2:178564558;178564557;178564556	chr2:179429285;179429284;179429283
Novex-2	18319	55180;55181;55182	chr2:178564558;178564557;178564556	chr2:179429285;179429284;179429283
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: Fn3-86
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.7519
• 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	rs1188322990	None	0.007	N	0.205	0.107	0.107399877778	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85925E-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	0.2395	likely_benign	0.2169	benign	-0.077	Destabilizing	0.373	N	0.427	neutral	None	None	None	None	N
K/C	0.6205	likely_pathogenic	0.6065	pathogenic	-0.218	Destabilizing	0.996	D	0.503	neutral	None	None	None	None	N
K/D	0.3423	ambiguous	0.3272	benign	0.059	Stabilizing	0.59	D	0.5	neutral	None	None	None	None	N
K/E	0.1142	likely_benign	0.1054	benign	0.083	Stabilizing	0.309	N	0.469	neutral	N	0.473303873	None	None	N
K/F	0.7267	likely_pathogenic	0.6918	pathogenic	-0.154	Destabilizing	0.953	D	0.522	neutral	None	None	None	None	N
K/G	0.3312	likely_benign	0.3098	benign	-0.317	Destabilizing	0.59	D	0.494	neutral	None	None	None	None	N
K/H	0.2832	likely_benign	0.2704	benign	-0.609	Destabilizing	0.953	D	0.555	neutral	None	None	None	None	N
K/I	0.3394	likely_benign	0.3086	benign	0.484	Stabilizing	0.91	D	0.556	neutral	None	None	None	None	N
K/L	0.2924	likely_benign	0.2664	benign	0.484	Stabilizing	0.59	D	0.491	neutral	None	None	None	None	N
K/M	0.1796	likely_benign	0.1655	benign	0.267	Stabilizing	0.939	D	0.557	neutral	N	0.519964456	None	None	N
K/N	0.2578	likely_benign	0.2351	benign	0.143	Stabilizing	0.007	N	0.205	neutral	N	0.498914393	None	None	N
K/P	0.6811	likely_pathogenic	0.6464	pathogenic	0.326	Stabilizing	0.953	D	0.596	neutral	None	None	None	None	N
K/Q	0.0976	likely_benign	0.0934	benign	-0.025	Destabilizing	0.028	N	0.269	neutral	N	0.488062681	None	None	N
K/R	0.0867	likely_benign	0.0853	benign	-0.146	Destabilizing	0.521	D	0.476	neutral	N	0.493065856	None	None	N
K/S	0.2636	likely_benign	0.239	benign	-0.374	Destabilizing	0.373	N	0.467	neutral	None	None	None	None	N
K/T	0.1045	likely_benign	0.0973	benign	-0.191	Destabilizing	0.004	N	0.237	neutral	N	0.388533192	None	None	N
K/V	0.2798	likely_benign	0.2548	benign	0.326	Stabilizing	0.59	D	0.535	neutral	None	None	None	None	N
K/W	0.7507	likely_pathogenic	0.728	pathogenic	-0.127	Destabilizing	0.996	D	0.518	neutral	None	None	None	None	N
K/Y	0.579	likely_pathogenic	0.5486	ambiguous	0.201	Stabilizing	0.984	D	0.552	neutral	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.