TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17409	52450;52451;52452	chr2:178608786;178608785;178608784	chr2:179473513;179473512;179473511
N2AB	15768	47527;47528;47529	chr2:178608786;178608785;178608784	chr2:179473513;179473512;179473511
N2A	14841	44746;44747;44748	chr2:178608786;178608785;178608784	chr2:179473513;179473512;179473511
N2B	8344	25255;25256;25257	chr2:178608786;178608785;178608784	chr2:179473513;179473512;179473511
Novex-1	8469	25630;25631;25632	chr2:178608786;178608785;178608784	chr2:179473513;179473512;179473511
Novex-2	8536	25831;25832;25833	chr2:178608786;178608785;178608784	chr2:179473513;179473512;179473511
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: Fn3-14
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0536
• 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/E	rs1203045644	-1.986	0.999	N	0.534	0.462	0.392855499163	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/E	rs1203045644	-1.986	0.999	N	0.534	0.462	0.392855499163	gnomAD-4.0.0	3.18747E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72377E-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	0.7115	likely_pathogenic	0.7501	pathogenic	-1.392	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
K/C	0.6779	likely_pathogenic	0.7006	pathogenic	-1.467	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
K/D	0.9817	likely_pathogenic	0.9847	pathogenic	-1.25	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/E	0.5822	likely_pathogenic	0.6226	pathogenic	-1.0	Destabilizing	0.999	D	0.534	neutral	N	0.472116027	None	None	N
K/F	0.9063	likely_pathogenic	0.93	pathogenic	-0.812	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
K/G	0.8711	likely_pathogenic	0.8902	pathogenic	-1.852	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/H	0.611	likely_pathogenic	0.6512	pathogenic	-1.977	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/I	0.6364	likely_pathogenic	0.6911	pathogenic	-0.116	Destabilizing	1.0	D	0.925	deleterious	N	0.494058623	None	None	N
K/L	0.5702	likely_pathogenic	0.6179	pathogenic	-0.116	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/M	0.2591	likely_benign	0.3086	benign	-0.337	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
K/N	0.8964	likely_pathogenic	0.9154	pathogenic	-1.481	Destabilizing	1.0	D	0.669	neutral	N	0.472662685	None	None	N
K/P	0.9979	likely_pathogenic	0.9975	pathogenic	-0.518	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
K/Q	0.1741	likely_benign	0.2006	benign	-1.285	Destabilizing	1.0	D	0.66	neutral	N	0.502279985	None	None	N
K/R	0.0967	likely_benign	0.092	benign	-0.991	Destabilizing	0.999	D	0.555	neutral	N	0.408561748	None	None	N
K/S	0.8673	likely_pathogenic	0.8914	pathogenic	-2.155	Highly Destabilizing	0.999	D	0.54	neutral	None	None	None	None	N
K/T	0.5884	likely_pathogenic	0.6229	pathogenic	-1.649	Destabilizing	1.0	D	0.78	deleterious	N	0.473890453	None	None	N
K/V	0.5954	likely_pathogenic	0.6327	pathogenic	-0.518	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
K/W	0.8917	likely_pathogenic	0.8995	pathogenic	-0.746	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
K/Y	0.7836	likely_pathogenic	0.8244	pathogenic	-0.408	Destabilizing	1.0	D	0.915	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.