TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22114	66565;66566;66567	chr2:178582029;178582028;178582027	chr2:179446756;179446755;179446754
N2AB	20473	61642;61643;61644	chr2:178582029;178582028;178582027	chr2:179446756;179446755;179446754
N2A	19546	58861;58862;58863	chr2:178582029;178582028;178582027	chr2:179446756;179446755;179446754
N2B	13049	39370;39371;39372	chr2:178582029;178582028;178582027	chr2:179446756;179446755;179446754
Novex-1	13174	39745;39746;39747	chr2:178582029;178582028;178582027	chr2:179446756;179446755;179446754
Novex-2	13241	39946;39947;39948	chr2:178582029;178582028;178582027	chr2:179446756;179446755;179446754
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-48
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.2713
• 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
T/I	rs1575927090	None	0.994	N	0.789	0.348	0.452928561435	gnomAD-4.0.0	4.77649E-06	None	None	None	None	N	None	0	0	None	0	8.32408E-05	None	0	0	0	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
T/A	0.21	likely_benign	0.183	benign	-0.854	Destabilizing	0.958	D	0.471	neutral	N	0.492969856	None	None	N
T/C	0.6072	likely_pathogenic	0.574	pathogenic	-0.469	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
T/D	0.8267	likely_pathogenic	0.7744	pathogenic	-0.008	Destabilizing	0.995	D	0.749	deleterious	None	None	None	None	N
T/E	0.7379	likely_pathogenic	0.6603	pathogenic	0.08	Stabilizing	0.991	D	0.696	prob.neutral	None	None	None	None	N
T/F	0.5848	likely_pathogenic	0.5298	ambiguous	-0.811	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
T/G	0.4501	ambiguous	0.4258	ambiguous	-1.183	Destabilizing	0.991	D	0.701	prob.neutral	None	None	None	None	N
T/H	0.499	ambiguous	0.4417	ambiguous	-1.307	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
T/I	0.4735	ambiguous	0.3909	ambiguous	-0.047	Destabilizing	0.994	D	0.789	deleterious	N	0.520137814	None	None	N
T/K	0.6173	likely_pathogenic	0.5419	ambiguous	-0.373	Destabilizing	0.919	D	0.598	neutral	N	0.503917568	None	None	N
T/L	0.3025	likely_benign	0.2523	benign	-0.047	Destabilizing	0.968	D	0.59	neutral	None	None	None	None	N
T/M	0.1919	likely_benign	0.1634	benign	-0.015	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/N	0.2425	likely_benign	0.2174	benign	-0.629	Destabilizing	0.991	D	0.68	prob.neutral	None	None	None	None	N
T/P	0.6616	likely_pathogenic	0.6316	pathogenic	-0.283	Destabilizing	0.998	D	0.785	deleterious	N	0.47325857	None	None	N
T/Q	0.4275	ambiguous	0.3727	ambiguous	-0.574	Destabilizing	0.991	D	0.794	deleterious	None	None	None	None	N
T/R	0.5467	ambiguous	0.4849	ambiguous	-0.355	Destabilizing	0.142	N	0.335	neutral	N	0.451699236	None	None	N
T/S	0.1885	likely_benign	0.1724	benign	-0.973	Destabilizing	0.958	D	0.431	neutral	N	0.432033253	None	None	N
T/V	0.3163	likely_benign	0.2658	benign	-0.283	Destabilizing	0.984	D	0.569	neutral	None	None	None	None	N
T/W	0.8613	likely_pathogenic	0.8431	pathogenic	-0.818	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/Y	0.542	ambiguous	0.4825	ambiguous	-0.506	Destabilizing	0.998	D	0.821	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.