TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6672	20239;20240;20241	chr2:178727351;178727350;178727349	chr2:179592078;179592077;179592076
N2AB	6355	19288;19289;19290	chr2:178727351;178727350;178727349	chr2:179592078;179592077;179592076
N2A	5428	16507;16508;16509	chr2:178727351;178727350;178727349	chr2:179592078;179592077;179592076
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-51
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.7367
• 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/I	None	None	0.216	N	0.718	0.172	0.407901774203	gnomAD-4.0.0	1.62345E-06	None	None	None	None	N	None	0	0	None	4.9034E-05	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	0.682	likely_pathogenic	0.7682	pathogenic	-0.425	Destabilizing	0.636	D	0.587	neutral	None	None	None	None	N
K/C	0.9158	likely_pathogenic	0.9358	pathogenic	-0.413	Destabilizing	0.993	D	0.73	prob.delet.	None	None	None	None	N
K/D	0.837	likely_pathogenic	0.8843	pathogenic	0.186	Stabilizing	0.466	N	0.603	neutral	None	None	None	None	N
K/E	0.464	ambiguous	0.611	pathogenic	0.282	Stabilizing	0.001	N	0.273	neutral	N	0.510176245	None	None	N
K/F	0.9214	likely_pathogenic	0.9327	pathogenic	-0.192	Destabilizing	0.938	D	0.708	prob.delet.	None	None	None	None	N
K/G	0.7366	likely_pathogenic	0.8066	pathogenic	-0.746	Destabilizing	0.636	D	0.577	neutral	None	None	None	None	N
K/H	0.5264	ambiguous	0.5614	ambiguous	-0.915	Destabilizing	0.951	D	0.679	prob.neutral	None	None	None	None	N
K/I	0.6897	likely_pathogenic	0.7415	pathogenic	0.386	Stabilizing	0.216	N	0.718	prob.delet.	N	0.456972788	None	None	N
K/L	0.632	likely_pathogenic	0.6811	pathogenic	0.386	Stabilizing	0.153	N	0.58	neutral	None	None	None	None	N
K/M	0.4414	ambiguous	0.524	ambiguous	0.081	Stabilizing	0.945	D	0.673	neutral	None	None	None	None	N
K/N	0.709	likely_pathogenic	0.7561	pathogenic	-0.142	Destabilizing	0.822	D	0.594	neutral	N	0.457703123	None	None	N
K/P	0.6155	likely_pathogenic	0.68	pathogenic	0.145	Stabilizing	0.925	D	0.676	prob.neutral	None	None	None	None	N
K/Q	0.2553	likely_benign	0.3271	benign	-0.177	Destabilizing	0.219	N	0.621	neutral	N	0.498825888	None	None	N
K/R	0.1093	likely_benign	0.1106	benign	-0.292	Destabilizing	0.001	N	0.22	neutral	N	0.504674424	None	None	N
K/S	0.76	likely_pathogenic	0.8201	pathogenic	-0.764	Destabilizing	0.636	D	0.587	neutral	None	None	None	None	N
K/T	0.454	ambiguous	0.5529	ambiguous	-0.47	Destabilizing	0.581	D	0.618	neutral	N	0.452249074	None	None	N
K/V	0.6539	likely_pathogenic	0.7053	pathogenic	0.145	Stabilizing	0.192	N	0.63	neutral	None	None	None	None	N
K/W	0.8976	likely_pathogenic	0.9136	pathogenic	-0.112	Destabilizing	0.995	D	0.73	prob.delet.	None	None	None	None	N
K/Y	0.8004	likely_pathogenic	0.8214	pathogenic	0.171	Stabilizing	0.638	D	0.717	prob.delet.	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.