TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7595	23008;23009;23010	chr2:178721880;178721879;178721878	chr2:179586607;179586606;179586605
N2AB	7278	22057;22058;22059	chr2:178721880;178721879;178721878	chr2:179586607;179586606;179586605
N2A	6351	19276;19277;19278	chr2:178721880;178721879;178721878	chr2:179586607;179586606;179586605
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-60
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.5443
• Predicted PPI site: I

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/Q	None	None	0.998	N	0.697	0.351	0.259272394797	gnomAD-4.0.0	1.59404E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86321E-06	0	0
K/R	rs2078423913	None	0.996	N	0.579	0.283	0.32980341726	gnomAD-4.0.0	1.59412E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86333E-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	0.4927	ambiguous	0.4248	ambiguous	-0.071	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	I
K/C	0.8509	likely_pathogenic	0.8282	pathogenic	-0.026	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
K/D	0.7275	likely_pathogenic	0.6832	pathogenic	0.026	Stabilizing	1.0	D	0.619	neutral	None	None	None	None	I
K/E	0.2163	likely_benign	0.1696	benign	0.056	Stabilizing	0.995	D	0.596	neutral	N	0.394838381	None	None	I
K/F	0.8682	likely_pathogenic	0.8226	pathogenic	-0.077	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
K/G	0.5991	likely_pathogenic	0.5452	ambiguous	-0.335	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	I
K/H	0.3953	ambiguous	0.3669	ambiguous	-0.673	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
K/I	0.5482	ambiguous	0.461	ambiguous	0.565	Stabilizing	0.992	D	0.684	prob.neutral	N	0.490138273	None	None	I
K/L	0.5645	likely_pathogenic	0.5007	ambiguous	0.565	Stabilizing	0.994	D	0.586	neutral	None	None	None	None	I
K/M	0.3385	likely_benign	0.276	benign	0.43	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	I
K/N	0.533	ambiguous	0.4781	ambiguous	0.273	Stabilizing	1.0	D	0.664	neutral	N	0.482980227	None	None	I
K/P	0.9404	likely_pathogenic	0.9353	pathogenic	0.383	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
K/Q	0.1559	likely_benign	0.1358	benign	0.087	Stabilizing	0.998	D	0.697	prob.neutral	N	0.426740156	None	None	I
K/R	0.0862	likely_benign	0.0867	benign	-0.104	Destabilizing	0.996	D	0.579	neutral	N	0.476707616	None	None	I
K/S	0.4679	ambiguous	0.4132	ambiguous	-0.247	Destabilizing	0.969	D	0.352	neutral	None	None	None	None	I
K/T	0.2244	likely_benign	0.1881	benign	-0.056	Destabilizing	0.989	D	0.64	neutral	N	0.4291271	None	None	I
K/V	0.4877	ambiguous	0.4088	ambiguous	0.383	Stabilizing	0.996	D	0.641	neutral	None	None	None	None	I
K/W	0.8284	likely_pathogenic	0.7834	pathogenic	-0.034	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
K/Y	0.754	likely_pathogenic	0.709	pathogenic	0.281	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I

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.