TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31055	93388;93389;93390	chr2:178548463;178548462;178548461	chr2:179413190;179413189;179413188
N2AB	29414	88465;88466;88467	chr2:178548463;178548462;178548461	chr2:179413190;179413189;179413188
N2A	28487	85684;85685;85686	chr2:178548463;178548462;178548461	chr2:179413190;179413189;179413188
N2B	21990	66193;66194;66195	chr2:178548463;178548462;178548461	chr2:179413190;179413189;179413188
Novex-1	22115	66568;66569;66570	chr2:178548463;178548462;178548461	chr2:179413190;179413189;179413188
Novex-2	22182	66769;66770;66771	chr2:178548463;178548462;178548461	chr2:179413190;179413189;179413188
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: Fn3-114
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2318
• 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	0.982	N	0.799	0.318	0.55810899713	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85802E-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	0.9032	likely_pathogenic	0.8892	pathogenic	-1.464	Destabilizing	0.953	D	0.645	neutral	None	None	None	None	N
K/C	0.8321	likely_pathogenic	0.8371	pathogenic	-1.665	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
K/D	0.9934	likely_pathogenic	0.9921	pathogenic	-2.689	Highly Destabilizing	0.993	D	0.65	neutral	None	None	None	None	N
K/E	0.8484	likely_pathogenic	0.8154	pathogenic	-2.36	Highly Destabilizing	0.939	D	0.679	prob.neutral	N	0.519605163	None	None	N
K/F	0.958	likely_pathogenic	0.9548	pathogenic	-0.711	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
K/G	0.9382	likely_pathogenic	0.9207	pathogenic	-1.935	Destabilizing	0.976	D	0.698	prob.neutral	None	None	None	None	N
K/H	0.717	likely_pathogenic	0.7219	pathogenic	-1.558	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
K/I	0.7804	likely_pathogenic	0.7907	pathogenic	-0.098	Destabilizing	0.982	D	0.799	deleterious	N	0.471822857	None	None	N
K/L	0.7299	likely_pathogenic	0.7268	pathogenic	-0.098	Destabilizing	0.953	D	0.689	prob.neutral	None	None	None	None	N
K/M	0.4972	ambiguous	0.4787	ambiguous	-0.566	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
K/N	0.959	likely_pathogenic	0.9522	pathogenic	-2.307	Highly Destabilizing	0.982	D	0.653	neutral	D	0.524378103	None	None	N
K/P	0.9985	likely_pathogenic	0.9978	pathogenic	-0.538	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
K/Q	0.3882	ambiguous	0.3622	ambiguous	-1.86	Destabilizing	0.982	D	0.657	neutral	N	0.499032146	None	None	N
K/R	0.121	likely_benign	0.1236	benign	-1.083	Destabilizing	0.1	N	0.508	neutral	N	0.496796808	None	None	N
K/S	0.9336	likely_pathogenic	0.9219	pathogenic	-2.68	Highly Destabilizing	0.91	D	0.656	neutral	None	None	None	None	N
K/T	0.772	likely_pathogenic	0.7577	pathogenic	-2.1	Highly Destabilizing	0.322	N	0.508	neutral	N	0.505006401	None	None	N
K/V	0.7339	likely_pathogenic	0.7545	pathogenic	-0.538	Destabilizing	0.986	D	0.697	prob.neutral	None	None	None	None	N
K/W	0.9378	likely_pathogenic	0.9367	pathogenic	-0.859	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
K/Y	0.8642	likely_pathogenic	0.8672	pathogenic	-0.513	Destabilizing	0.998	D	0.77	deleterious	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.