TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15426	46501;46502;46503	chr2:178620245;178620244;178620243	chr2:179484972;179484971;179484970
N2AB	13785	41578;41579;41580	chr2:178620245;178620244;178620243	chr2:179484972;179484971;179484970
N2A	12858	38797;38798;38799	chr2:178620245;178620244;178620243	chr2:179484972;179484971;179484970
N2B	6361	19306;19307;19308	chr2:178620245;178620244;178620243	chr2:179484972;179484971;179484970
Novex-1	6486	19681;19682;19683	chr2:178620245;178620244;178620243	chr2:179484972;179484971;179484970
Novex-2	6553	19882;19883;19884	chr2:178620245;178620244;178620243	chr2:179484972;179484971;179484970
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-106
• Domain position: 36
• Structural Position: 51
• Q(SASA): 0.6371
• 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/Y	rs763751237	-0.604	0.963	D	0.468	0.61	0.709004203348	gnomAD-2.1.1	1.06E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.19E-05	0
N/Y	rs763751237	-0.604	0.963	D	0.468	0.61	0.709004203348	gnomAD-4.0.0	5.76349E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.40997E-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	0.6484	likely_pathogenic	0.6731	pathogenic	-0.559	Destabilizing	0.447	N	0.439	neutral	None	None	None	None	N
N/C	0.6649	likely_pathogenic	0.6705	pathogenic	0.257	Stabilizing	0.992	D	0.489	neutral	None	None	None	None	N
N/D	0.2427	likely_benign	0.2759	benign	0.121	Stabilizing	0.002	N	0.149	neutral	N	0.505806137	None	None	N
N/E	0.7759	likely_pathogenic	0.785	pathogenic	0.137	Stabilizing	0.447	N	0.393	neutral	None	None	None	None	N
N/F	0.8995	likely_pathogenic	0.9243	pathogenic	-0.665	Destabilizing	0.92	D	0.478	neutral	None	None	None	None	N
N/G	0.4591	ambiguous	0.466	ambiguous	-0.807	Destabilizing	0.25	N	0.387	neutral	None	None	None	None	N
N/H	0.3537	ambiguous	0.3578	ambiguous	-0.733	Destabilizing	0.963	D	0.447	neutral	D	0.732593773	None	None	N
N/I	0.8974	likely_pathogenic	0.9243	pathogenic	0.025	Stabilizing	0.681	D	0.485	neutral	D	0.732317958	None	None	N
N/K	0.7702	likely_pathogenic	0.7645	pathogenic	-0.056	Destabilizing	0.549	D	0.397	neutral	D	0.588093169	None	None	N
N/L	0.7447	likely_pathogenic	0.7794	pathogenic	0.025	Stabilizing	0.447	N	0.447	neutral	None	None	None	None	N
N/M	0.8044	likely_pathogenic	0.8378	pathogenic	0.346	Stabilizing	0.977	D	0.463	neutral	None	None	None	None	N
N/P	0.9887	likely_pathogenic	0.9909	pathogenic	-0.141	Destabilizing	0.92	D	0.457	neutral	None	None	None	None	N
N/Q	0.6899	likely_pathogenic	0.6803	pathogenic	-0.465	Destabilizing	0.92	D	0.413	neutral	None	None	None	None	N
N/R	0.7625	likely_pathogenic	0.757	pathogenic	-0.069	Destabilizing	0.85	D	0.397	neutral	None	None	None	None	N
N/S	0.1945	likely_benign	0.2062	benign	-0.382	Destabilizing	0.016	N	0.194	neutral	D	0.647419644	None	None	N
N/T	0.6771	likely_pathogenic	0.7499	pathogenic	-0.196	Destabilizing	0.004	N	0.225	neutral	D	0.733428974	None	None	N
N/V	0.871	likely_pathogenic	0.9053	pathogenic	-0.141	Destabilizing	0.739	D	0.429	neutral	None	None	None	None	N
N/W	0.9485	likely_pathogenic	0.9558	pathogenic	-0.554	Destabilizing	0.992	D	0.567	neutral	None	None	None	None	N
N/Y	0.464	ambiguous	0.5065	ambiguous	-0.332	Destabilizing	0.963	D	0.468	neutral	D	0.695494244	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.