TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21870	65833;65834;65835	chr2:178583195;178583194;178583193	chr2:179447922;179447921;179447920
N2AB	20229	60910;60911;60912	chr2:178583195;178583194;178583193	chr2:179447922;179447921;179447920
N2A	19302	58129;58130;58131	chr2:178583195;178583194;178583193	chr2:179447922;179447921;179447920
N2B	12805	38638;38639;38640	chr2:178583195;178583194;178583193	chr2:179447922;179447921;179447920
Novex-1	12930	39013;39014;39015	chr2:178583195;178583194;178583193	chr2:179447922;179447921;179447920
Novex-2	12997	39214;39215;39216	chr2:178583195;178583194;178583193	chr2:179447922;179447921;179447920
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-125
• Domain position: 5
• Structural Position: 8
• Q(SASA): 0.5329
• 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/I	None	None	0.82	N	0.692	0.283	0.489036454283	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
K/N	None	None	0.901	N	0.628	0.156	0.177238962908	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	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	0.6005	likely_pathogenic	0.5336	ambiguous	0.031	Stabilizing	0.775	D	0.653	neutral	None	None	None	None	N
K/C	0.8733	likely_pathogenic	0.8327	pathogenic	-0.366	Destabilizing	0.996	D	0.729	prob.delet.	None	None	None	None	N
K/D	0.7803	likely_pathogenic	0.7321	pathogenic	-0.023	Destabilizing	0.923	D	0.669	neutral	None	None	None	None	N
K/E	0.3751	ambiguous	0.3152	benign	-0.035	Destabilizing	0.565	D	0.648	neutral	N	0.510273111	None	None	N
K/F	0.9438	likely_pathogenic	0.9229	pathogenic	-0.319	Destabilizing	0.923	D	0.711	prob.delet.	None	None	None	None	N
K/G	0.622	likely_pathogenic	0.5559	ambiguous	-0.107	Destabilizing	0.775	D	0.641	neutral	None	None	None	None	N
K/H	0.4664	ambiguous	0.4321	ambiguous	-0.286	Destabilizing	0.989	D	0.686	prob.neutral	None	None	None	None	N
K/I	0.7431	likely_pathogenic	0.6847	pathogenic	0.306	Stabilizing	0.82	D	0.692	prob.neutral	N	0.52158897	None	None	N
K/L	0.6358	likely_pathogenic	0.5858	pathogenic	0.306	Stabilizing	0.011	N	0.406	neutral	None	None	None	None	N
K/M	0.4961	ambiguous	0.4508	ambiguous	0.063	Stabilizing	0.923	D	0.697	prob.neutral	None	None	None	None	N
K/N	0.5896	likely_pathogenic	0.5314	ambiguous	0.113	Stabilizing	0.901	D	0.628	neutral	N	0.515873719	None	None	N
K/P	0.8873	likely_pathogenic	0.8501	pathogenic	0.239	Stabilizing	0.961	D	0.7	prob.neutral	None	None	None	None	N
K/Q	0.1803	likely_benign	0.159	benign	-0.041	Destabilizing	0.075	N	0.301	neutral	N	0.485377454	None	None	N
K/R	0.1114	likely_benign	0.1041	benign	-0.031	Destabilizing	0.008	N	0.299	neutral	N	0.473525664	None	None	N
K/S	0.6337	likely_pathogenic	0.5752	pathogenic	-0.319	Destabilizing	0.775	D	0.606	neutral	None	None	None	None	N
K/T	0.3408	ambiguous	0.291	benign	-0.203	Destabilizing	0.722	D	0.667	neutral	N	0.492284783	None	None	N
K/V	0.6676	likely_pathogenic	0.608	pathogenic	0.239	Stabilizing	0.633	D	0.639	neutral	None	None	None	None	N
K/W	0.9239	likely_pathogenic	0.9028	pathogenic	-0.392	Destabilizing	0.996	D	0.735	prob.delet.	None	None	None	None	N
K/Y	0.8424	likely_pathogenic	0.8051	pathogenic	-0.021	Destabilizing	0.961	D	0.711	prob.delet.	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.