TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7358	22297;22298;22299	chr2:178722827;178722826;178722825	chr2:179587554;179587553;179587552
N2AB	7041	21346;21347;21348	chr2:178722827;178722826;178722825	chr2:179587554;179587553;179587552
N2A	6114	18565;18566;18567	chr2:178722827;178722826;178722825	chr2:179587554;179587553;179587552
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-58
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2466
• 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/R	rs1271277715	-0.508	0.999	N	0.511	0.269	0.201204373187	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/R	rs1271277715	-0.508	0.999	N	0.511	0.269	0.201204373187	gnomAD-4.0.0	1.59235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85992E-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	0.8907	likely_pathogenic	0.9568	pathogenic	-0.923	Destabilizing	1.0	D	0.545	neutral	None	None	None	None	N
K/C	0.9243	likely_pathogenic	0.9576	pathogenic	-0.894	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/D	0.9697	likely_pathogenic	0.9905	pathogenic	0.295	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/E	0.7134	likely_pathogenic	0.8773	pathogenic	0.423	Stabilizing	0.998	D	0.457	neutral	D	0.53076675	None	None	N
K/F	0.9456	likely_pathogenic	0.9693	pathogenic	-0.784	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/G	0.9472	likely_pathogenic	0.9805	pathogenic	-1.264	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/H	0.5491	ambiguous	0.6675	pathogenic	-1.537	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/I	0.7875	likely_pathogenic	0.8782	pathogenic	-0.038	Destabilizing	0.999	D	0.77	deleterious	N	0.503001257	None	None	N
K/L	0.7351	likely_pathogenic	0.8376	pathogenic	-0.038	Destabilizing	0.998	D	0.652	neutral	None	None	None	None	N
K/M	0.6564	likely_pathogenic	0.7853	pathogenic	-0.137	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/N	0.9101	likely_pathogenic	0.9628	pathogenic	-0.383	Destabilizing	0.984	D	0.306	neutral	N	0.49627976	None	None	N
K/P	0.9954	likely_pathogenic	0.9984	pathogenic	-0.305	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
K/Q	0.3777	ambiguous	0.544	ambiguous	-0.437	Destabilizing	0.999	D	0.572	neutral	N	0.487872743	None	None	N
K/R	0.0931	likely_benign	0.1125	benign	-0.4	Destabilizing	0.999	D	0.511	neutral	N	0.468276481	None	None	N
K/S	0.9071	likely_pathogenic	0.9661	pathogenic	-1.226	Destabilizing	1.0	D	0.465	neutral	None	None	None	None	N
K/T	0.8142	likely_pathogenic	0.9183	pathogenic	-0.876	Destabilizing	1.0	D	0.652	neutral	N	0.498330449	None	None	N
K/V	0.7734	likely_pathogenic	0.8688	pathogenic	-0.305	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
K/W	0.9221	likely_pathogenic	0.9605	pathogenic	-0.577	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/Y	0.8656	likely_pathogenic	0.9177	pathogenic	-0.274	Destabilizing	1.0	D	0.757	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.