TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4735	14428;14429;14430	chr2:178738250;178738249;178738248	chr2:179602977;179602976;179602975
N2AB	4418	13477;13478;13479	chr2:178738250;178738249;178738248	chr2:179602977;179602976;179602975
N2A	3491	10696;10697;10698	chr2:178738250;178738249;178738248	chr2:179602977;179602976;179602975
N2B	4372	13339;13340;13341	chr2:178738250;178738249;178738248	chr2:179602977;179602976;179602975
Novex-1	4497	13714;13715;13716	chr2:178738250;178738249;178738248	chr2:179602977;179602976;179602975
Novex-2	4564	13915;13916;13917	chr2:178738250;178738249;178738248	chr2:179602977;179602976;179602975
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-30
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2205
• 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	None	None	0.977	D	0.476	0.516	0.345405024496	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9796	likely_pathogenic	0.9819	pathogenic	-0.863	Destabilizing	0.983	D	0.574	neutral	None	None	None	None	N
K/C	0.9622	likely_pathogenic	0.9714	pathogenic	-0.75	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
K/D	0.9973	likely_pathogenic	0.9974	pathogenic	0.033	Stabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
K/E	0.9639	likely_pathogenic	0.9664	pathogenic	0.172	Stabilizing	0.977	D	0.476	neutral	D	0.727208055	None	None	N
K/F	0.982	likely_pathogenic	0.9824	pathogenic	-0.572	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/G	0.988	likely_pathogenic	0.9889	pathogenic	-1.242	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
K/H	0.7318	likely_pathogenic	0.7424	pathogenic	-1.571	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
K/I	0.9535	likely_pathogenic	0.9596	pathogenic	0.133	Stabilizing	0.997	D	0.835	deleterious	D	0.637618849	None	None	N
K/L	0.8957	likely_pathogenic	0.9183	pathogenic	0.133	Stabilizing	0.995	D	0.733	prob.delet.	None	None	None	None	N
K/M	0.9007	likely_pathogenic	0.9095	pathogenic	0.029	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/N	0.9873	likely_pathogenic	0.9881	pathogenic	-0.501	Destabilizing	0.993	D	0.668	neutral	D	0.589326464	None	None	N
K/P	0.9978	likely_pathogenic	0.9975	pathogenic	-0.17	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
K/Q	0.7143	likely_pathogenic	0.7409	pathogenic	-0.519	Destabilizing	0.993	D	0.654	neutral	D	0.612669518	None	None	N
K/R	0.1041	likely_benign	0.1209	benign	-0.578	Destabilizing	0.235	N	0.313	neutral	N	0.463761901	None	None	N
K/S	0.9868	likely_pathogenic	0.9883	pathogenic	-1.262	Destabilizing	0.983	D	0.544	neutral	None	None	None	None	N
K/T	0.9676	likely_pathogenic	0.9675	pathogenic	-0.896	Destabilizing	0.997	D	0.74	deleterious	D	0.599466738	None	None	N
K/V	0.9375	likely_pathogenic	0.9494	pathogenic	-0.17	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
K/W	0.9718	likely_pathogenic	0.9713	pathogenic	-0.407	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/Y	0.9469	likely_pathogenic	0.9492	pathogenic	-0.113	Destabilizing	0.999	D	0.825	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.