TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6834	20725;20726;20727	chr2:178725822;178725821;178725820	chr2:179590549;179590548;179590547
N2AB	6517	19774;19775;19776	chr2:178725822;178725821;178725820	chr2:179590549;179590548;179590547
N2A	5590	16993;16994;16995	chr2:178725822;178725821;178725820	chr2:179590549;179590548;179590547
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-52
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.3335
• 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	None	None	0.645	N	0.554	0.161	0.166414681773	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.7321	likely_pathogenic	0.6802	pathogenic	-0.874	Destabilizing	0.498	N	0.515	neutral	None	None	None	None	N
K/C	0.8939	likely_pathogenic	0.8546	pathogenic	-1.065	Destabilizing	0.995	D	0.637	neutral	None	None	None	None	N
K/D	0.9342	likely_pathogenic	0.9194	pathogenic	-0.909	Destabilizing	0.706	D	0.592	neutral	None	None	None	None	N
K/E	0.4684	ambiguous	0.405	ambiguous	-0.724	Destabilizing	0.101	N	0.535	neutral	N	0.503352713	None	None	N
K/F	0.8956	likely_pathogenic	0.855	pathogenic	-0.357	Destabilizing	0.954	D	0.645	neutral	None	None	None	None	N
K/G	0.8953	likely_pathogenic	0.8706	pathogenic	-1.305	Destabilizing	0.706	D	0.627	neutral	None	None	None	None	N
K/H	0.5059	ambiguous	0.4607	ambiguous	-1.659	Destabilizing	0.877	D	0.593	neutral	None	None	None	None	N
K/I	0.4548	ambiguous	0.3821	ambiguous	0.287	Stabilizing	0.158	N	0.669	neutral	N	0.47691826	None	None	N
K/L	0.5744	likely_pathogenic	0.5072	ambiguous	0.287	Stabilizing	0.066	N	0.631	neutral	None	None	None	None	N
K/M	0.4011	ambiguous	0.3316	benign	0.057	Stabilizing	0.862	D	0.589	neutral	None	None	None	None	N
K/N	0.8374	likely_pathogenic	0.8002	pathogenic	-1.141	Destabilizing	0.645	D	0.554	neutral	N	0.517148729	None	None	N
K/P	0.9931	likely_pathogenic	0.9929	pathogenic	-0.072	Destabilizing	0.981	D	0.61	neutral	None	None	None	None	N
K/Q	0.2449	likely_benign	0.2179	benign	-1.058	Destabilizing	0.008	N	0.351	neutral	N	0.496290667	None	None	N
K/R	0.1005	likely_benign	0.0985	benign	-0.987	Destabilizing	None	N	0.222	neutral	N	0.500389765	None	None	N
K/S	0.8081	likely_pathogenic	0.7621	pathogenic	-1.726	Destabilizing	0.332	N	0.521	neutral	None	None	None	None	N
K/T	0.3919	ambiguous	0.338	benign	-1.312	Destabilizing	0.003	N	0.343	neutral	N	0.486401748	None	None	N
K/V	0.4405	ambiguous	0.3803	ambiguous	-0.072	Destabilizing	0.085	N	0.623	neutral	None	None	None	None	N
K/W	0.9097	likely_pathogenic	0.8737	pathogenic	-0.327	Destabilizing	0.997	D	0.649	neutral	None	None	None	None	N
K/Y	0.8314	likely_pathogenic	0.788	pathogenic	0.016	Stabilizing	0.708	D	0.647	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.