TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18417	55474;55475;55476	chr2:178602022;178602021;178602020	chr2:179466749;179466748;179466747
N2AB	16776	50551;50552;50553	chr2:178602022;178602021;178602020	chr2:179466749;179466748;179466747
N2A	15849	47770;47771;47772	chr2:178602022;178602021;178602020	chr2:179466749;179466748;179466747
N2B	9352	28279;28280;28281	chr2:178602022;178602021;178602020	chr2:179466749;179466748;179466747
Novex-1	9477	28654;28655;28656	chr2:178602022;178602021;178602020	chr2:179466749;179466748;179466747
Novex-2	9544	28855;28856;28857	chr2:178602022;178602021;178602020	chr2:179466749;179466748;179466747
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-115
• Domain position: 36
• Structural Position: 55
• Q(SASA): 0.226
• 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	rs1282114647	-0.196	0.968	N	0.51	0.28	0.289098819767	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
K/N	rs1282114647	-0.196	0.968	N	0.51	0.28	0.289098819767	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs1282114647	-0.196	0.968	N	0.51	0.28	0.289098819767	gnomAD-4.0.0	3.84873E-06	None	None	None	None	N	None	5.08406E-05	0	None	0	0	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	0.2499	likely_benign	0.244	benign	-0.011	Destabilizing	0.034	N	0.278	neutral	None	None	None	None	N
K/C	0.6152	likely_pathogenic	0.625	pathogenic	-0.361	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
K/D	0.3959	ambiguous	0.3882	ambiguous	0.111	Stabilizing	0.851	D	0.501	neutral	None	None	None	None	N
K/E	0.1633	likely_benign	0.1613	benign	0.097	Stabilizing	0.026	N	0.271	neutral	N	0.498098822	None	None	N
K/F	0.6595	likely_pathogenic	0.6683	pathogenic	-0.373	Destabilizing	0.996	D	0.726	prob.delet.	None	None	None	None	N
K/G	0.3418	ambiguous	0.3441	ambiguous	-0.144	Destabilizing	0.851	D	0.543	neutral	None	None	None	None	N
K/H	0.2891	likely_benign	0.2842	benign	-0.354	Destabilizing	0.997	D	0.625	neutral	None	None	None	None	N
K/I	0.272	likely_benign	0.2748	benign	0.248	Stabilizing	0.976	D	0.734	prob.delet.	None	None	None	None	N
K/L	0.2889	likely_benign	0.2939	benign	0.248	Stabilizing	0.919	D	0.541	neutral	None	None	None	None	N
K/M	0.2169	likely_benign	0.2196	benign	0.059	Stabilizing	0.999	D	0.618	neutral	D	0.526731005	None	None	N
K/N	0.2831	likely_benign	0.2816	benign	0.155	Stabilizing	0.968	D	0.51	neutral	N	0.521015754	None	None	N
K/P	0.4695	ambiguous	0.4685	ambiguous	0.186	Stabilizing	0.988	D	0.628	neutral	None	None	None	None	N
K/Q	0.1365	likely_benign	0.1353	benign	-0.007	Destabilizing	0.938	D	0.5	neutral	N	0.505198152	None	None	N
K/R	0.095	likely_benign	0.0953	benign	-0.018	Destabilizing	0.896	D	0.447	neutral	N	0.520669037	None	None	N
K/S	0.3048	likely_benign	0.2921	benign	-0.308	Destabilizing	0.851	D	0.448	neutral	None	None	None	None	N
K/T	0.1496	likely_benign	0.1384	benign	-0.193	Destabilizing	0.896	D	0.511	neutral	N	0.48690318	None	None	N
K/V	0.2414	likely_benign	0.2431	benign	0.186	Stabilizing	0.952	D	0.576	neutral	None	None	None	None	N
K/W	0.7506	likely_pathogenic	0.7599	pathogenic	-0.426	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
K/Y	0.5657	likely_pathogenic	0.5796	pathogenic	-0.055	Destabilizing	0.996	D	0.697	prob.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.