TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15792	47599;47600;47601	chr2:178617977;178617976;178617975	chr2:179482704;179482703;179482702
N2AB	14151	42676;42677;42678	chr2:178617977;178617976;178617975	chr2:179482704;179482703;179482702
N2A	13224	39895;39896;39897	chr2:178617977;178617976;178617975	chr2:179482704;179482703;179482702
N2B	6727	20404;20405;20406	chr2:178617977;178617976;178617975	chr2:179482704;179482703;179482702
Novex-1	6852	20779;20780;20781	chr2:178617977;178617976;178617975	chr2:179482704;179482703;179482702
Novex-2	6919	20980;20981;20982	chr2:178617977;178617976;178617975	chr2:179482704;179482703;179482702
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-2
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1418
• 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
N/D	None	None	0.183	N	0.35	0.123	0.130388298395	gnomAD-4.0.0	1.5935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86269E-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
N/A	0.1682	likely_benign	0.1449	benign	-1.046	Destabilizing	0.001	N	0.521	neutral	None	None	None	None	N
N/C	0.2591	likely_benign	0.2041	benign	-0.374	Destabilizing	0.836	D	0.699	prob.neutral	None	None	None	None	N
N/D	0.1358	likely_benign	0.1142	benign	-1.323	Destabilizing	0.183	N	0.35	neutral	N	0.482665372	None	None	N
N/E	0.353	ambiguous	0.2981	benign	-1.191	Destabilizing	0.228	N	0.341	neutral	None	None	None	None	N
N/F	0.6389	likely_pathogenic	0.5474	ambiguous	-0.779	Destabilizing	0.836	D	0.736	prob.delet.	None	None	None	None	N
N/G	0.151	likely_benign	0.1343	benign	-1.389	Destabilizing	None	N	0.115	neutral	None	None	None	None	N
N/H	0.115	likely_benign	0.1002	benign	-0.994	Destabilizing	0.921	D	0.558	neutral	N	0.473031458	None	None	N
N/I	0.5207	ambiguous	0.4561	ambiguous	-0.16	Destabilizing	0.655	D	0.769	deleterious	N	0.479012032	None	None	N
N/K	0.382	ambiguous	0.329	benign	-0.324	Destabilizing	0.183	N	0.339	neutral	N	0.438625419	None	None	N
N/L	0.3691	ambiguous	0.3228	benign	-0.16	Destabilizing	0.264	N	0.687	prob.neutral	None	None	None	None	N
N/M	0.4481	ambiguous	0.3857	ambiguous	0.267	Stabilizing	0.94	D	0.677	prob.neutral	None	None	None	None	N
N/P	0.9768	likely_pathogenic	0.9692	pathogenic	-0.427	Destabilizing	0.593	D	0.718	prob.delet.	None	None	None	None	N
N/Q	0.3084	likely_benign	0.2554	benign	-1.106	Destabilizing	0.593	D	0.539	neutral	None	None	None	None	N
N/R	0.3369	likely_benign	0.2846	benign	-0.265	Destabilizing	0.418	N	0.487	neutral	None	None	None	None	N
N/S	0.0612	likely_benign	0.0598	benign	-1.112	Destabilizing	0.003	N	0.113	neutral	N	0.42098344	None	None	N
N/T	0.1438	likely_benign	0.1293	benign	-0.796	Destabilizing	0.101	N	0.337	neutral	N	0.4797167	None	None	N
N/V	0.4319	ambiguous	0.3634	ambiguous	-0.427	Destabilizing	0.264	N	0.691	prob.neutral	None	None	None	None	N
N/W	0.7981	likely_pathogenic	0.7436	pathogenic	-0.526	Destabilizing	0.983	D	0.722	prob.delet.	None	None	None	None	N
N/Y	0.2272	likely_benign	0.1911	benign	-0.273	Destabilizing	0.921	D	0.709	prob.delet.	N	0.477614246	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.