TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28987	87184;87185;87186	chr2:178558500;178558499;178558498	chr2:179423227;179423226;179423225
N2AB	27346	82261;82262;82263	chr2:178558500;178558499;178558498	chr2:179423227;179423226;179423225
N2A	26419	79480;79481;79482	chr2:178558500;178558499;178558498	chr2:179423227;179423226;179423225
N2B	19922	59989;59990;59991	chr2:178558500;178558499;178558498	chr2:179423227;179423226;179423225
Novex-1	20047	60364;60365;60366	chr2:178558500;178558499;178558498	chr2:179423227;179423226;179423225
Novex-2	20114	60565;60566;60567	chr2:178558500;178558499;178558498	chr2:179423227;179423226;179423225
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-99
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.0205
• 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/R	rs1186947794	0.179	0.012	N	0.385	0.082	0.30212335484	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/R	rs1186947794	0.179	0.012	N	0.385	0.082	0.30212335484	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs1186947794	0.179	0.012	N	0.385	0.082	0.30212335484	gnomAD-4.0.0	5.12438E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.17851E-06	1.33994E-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
K/A	0.2049	likely_benign	0.174	benign	-0.025	Destabilizing	0.016	N	0.459	neutral	None	None	None	None	N
K/C	0.5002	ambiguous	0.4998	ambiguous	-0.531	Destabilizing	0.676	D	0.279	neutral	None	None	None	None	N
K/D	0.2532	likely_benign	0.231	benign	-0.368	Destabilizing	0.016	N	0.44	neutral	None	None	None	None	N
K/E	0.1026	likely_benign	0.0908	benign	-0.387	Destabilizing	None	N	0.137	neutral	N	0.383663303	None	None	N
K/F	0.6214	likely_pathogenic	0.6082	pathogenic	-0.394	Destabilizing	0.356	N	0.308	neutral	None	None	None	None	N
K/G	0.2028	likely_benign	0.1933	benign	-0.132	Destabilizing	0.031	N	0.307	neutral	None	None	None	None	N
K/H	0.2294	likely_benign	0.2299	benign	-0.186	Destabilizing	0.356	N	0.373	neutral	None	None	None	None	N
K/I	0.2942	likely_benign	0.2617	benign	0.176	Stabilizing	0.093	N	0.338	neutral	N	0.468668844	None	None	N
K/L	0.2431	likely_benign	0.2268	benign	0.176	Stabilizing	0.016	N	0.308	neutral	None	None	None	None	N
K/M	0.1846	likely_benign	0.1721	benign	-0.191	Destabilizing	0.356	N	0.371	neutral	None	None	None	None	N
K/N	0.1837	likely_benign	0.1693	benign	-0.066	Destabilizing	0.055	N	0.365	neutral	N	0.398171396	None	None	N
K/P	0.288	likely_benign	0.2536	benign	0.13	Stabilizing	0.136	N	0.391	neutral	None	None	None	None	N
K/Q	0.0961	likely_benign	0.0896	benign	-0.207	Destabilizing	None	N	0.137	neutral	N	0.409561825	None	None	N
K/R	0.081	likely_benign	0.0823	benign	-0.152	Destabilizing	0.012	N	0.385	neutral	N	0.431323964	None	None	N
K/S	0.2076	likely_benign	0.1836	benign	-0.412	Destabilizing	0.016	N	0.401	neutral	None	None	None	None	N
K/T	0.1241	likely_benign	0.1045	benign	-0.324	Destabilizing	None	N	0.223	neutral	N	0.419778819	None	None	N
K/V	0.2496	likely_benign	0.2207	benign	0.13	Stabilizing	0.038	N	0.329	neutral	None	None	None	None	N
K/W	0.584	likely_pathogenic	0.6114	pathogenic	-0.508	Destabilizing	0.864	D	0.269	neutral	None	None	None	None	N
K/Y	0.4606	ambiguous	0.4672	ambiguous	-0.163	Destabilizing	0.356	N	0.339	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.