TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20763	62512;62513;62514	chr2:178589438;178589437;178589436	chr2:179454165;179454164;179454163
N2AB	19122	57589;57590;57591	chr2:178589438;178589437;178589436	chr2:179454165;179454164;179454163
N2A	18195	54808;54809;54810	chr2:178589438;178589437;178589436	chr2:179454165;179454164;179454163
N2B	11698	35317;35318;35319	chr2:178589438;178589437;178589436	chr2:179454165;179454164;179454163
Novex-1	11823	35692;35693;35694	chr2:178589438;178589437;178589436	chr2:179454165;179454164;179454163
Novex-2	11890	35893;35894;35895	chr2:178589438;178589437;178589436	chr2:179454165;179454164;179454163
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: Fn3-38
• Domain position: 96
• Structural Position: 130
• Q(SASA): 0.0492
• 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/T	None	None	0.999	N	0.765	0.322	0.358744678677	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.7543	likely_pathogenic	0.7915	pathogenic	-0.469	Destabilizing	0.997	D	0.661	prob.neutral	None	None	None	None	N
K/C	0.8788	likely_pathogenic	0.8948	pathogenic	-0.489	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/D	0.9416	likely_pathogenic	0.962	pathogenic	-0.474	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
K/E	0.5567	ambiguous	0.5991	pathogenic	-0.348	Destabilizing	0.991	D	0.562	neutral	N	0.471312197	None	None	N
K/F	0.9614	likely_pathogenic	0.9713	pathogenic	0.045	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/G	0.8416	likely_pathogenic	0.8764	pathogenic	-0.869	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
K/H	0.6319	likely_pathogenic	0.6503	pathogenic	-1.288	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/I	0.8079	likely_pathogenic	0.8182	pathogenic	0.586	Stabilizing	1.0	D	0.814	deleterious	N	0.520092168	None	None	N
K/L	0.7278	likely_pathogenic	0.7894	pathogenic	0.586	Stabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
K/M	0.5675	likely_pathogenic	0.618	pathogenic	0.445	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
K/N	0.8777	likely_pathogenic	0.9103	pathogenic	-0.666	Destabilizing	0.999	D	0.74	deleterious	N	0.490176921	None	None	N
K/P	0.9831	likely_pathogenic	0.9907	pathogenic	0.265	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
K/Q	0.2598	likely_benign	0.2725	benign	-0.67	Destabilizing	0.999	D	0.727	deleterious	N	0.506528225	None	None	N
K/R	0.1026	likely_benign	0.1035	benign	-0.909	Destabilizing	0.779	D	0.301	neutral	N	0.506874942	None	None	N
K/S	0.8198	likely_pathogenic	0.8548	pathogenic	-1.192	Destabilizing	0.997	D	0.606	neutral	None	None	None	None	N
K/T	0.5141	ambiguous	0.5257	ambiguous	-0.863	Destabilizing	0.999	D	0.765	deleterious	N	0.466285768	None	None	N
K/V	0.7092	likely_pathogenic	0.7095	pathogenic	0.265	Stabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
K/W	0.9359	likely_pathogenic	0.9467	pathogenic	0.098	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
K/Y	0.9182	likely_pathogenic	0.939	pathogenic	0.369	Stabilizing	1.0	D	0.813	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.