TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17808	53647;53648;53649	chr2:178607180;178607179;178607178	chr2:179471907;179471906;179471905
N2AB	16167	48724;48725;48726	chr2:178607180;178607179;178607178	chr2:179471907;179471906;179471905
N2A	15240	45943;45944;45945	chr2:178607180;178607179;178607178	chr2:179471907;179471906;179471905
N2B	8743	26452;26453;26454	chr2:178607180;178607179;178607178	chr2:179471907;179471906;179471905
Novex-1	8868	26827;26828;26829	chr2:178607180;178607179;178607178	chr2:179471907;179471906;179471905
Novex-2	8935	27028;27029;27030	chr2:178607180;178607179;178607178	chr2:179471907;179471906;179471905
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-17
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2047
• 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
M/I	rs1018984134	None	0.454	N	0.303	0.226	0.436025050644	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	4.78927E-04
M/I	rs1018984134	None	0.454	N	0.303	0.226	0.436025050644	gnomAD-4.0.0	3.0998E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39189E-06	0	1.60174E-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
M/A	0.6687	likely_pathogenic	0.6742	pathogenic	-1.095	Destabilizing	0.007	N	0.144	neutral	None	None	None	None	N
M/C	0.7817	likely_pathogenic	0.8558	pathogenic	-0.333	Destabilizing	0.991	D	0.31	neutral	None	None	None	None	N
M/D	0.9392	likely_pathogenic	0.9551	pathogenic	-0.13	Destabilizing	0.974	D	0.442	neutral	None	None	None	None	N
M/E	0.8415	likely_pathogenic	0.8537	pathogenic	-0.181	Destabilizing	0.842	D	0.369	neutral	None	None	None	None	N
M/F	0.4973	ambiguous	0.5424	ambiguous	-0.635	Destabilizing	0.949	D	0.303	neutral	None	None	None	None	N
M/G	0.773	likely_pathogenic	0.7995	pathogenic	-1.295	Destabilizing	0.728	D	0.349	neutral	None	None	None	None	N
M/H	0.7112	likely_pathogenic	0.7676	pathogenic	-0.442	Destabilizing	0.998	D	0.384	neutral	None	None	None	None	N
M/I	0.8019	likely_pathogenic	0.8274	pathogenic	-0.635	Destabilizing	0.454	N	0.303	neutral	N	0.469367322	None	None	N
M/K	0.6667	likely_pathogenic	0.6693	pathogenic	-0.006	Destabilizing	0.801	D	0.311	neutral	N	0.452984528	None	None	N
M/L	0.3186	likely_benign	0.3163	benign	-0.635	Destabilizing	0.005	N	0.131	neutral	N	0.512187548	None	None	N
M/N	0.6138	likely_pathogenic	0.6665	pathogenic	0.302	Stabilizing	0.974	D	0.421	neutral	None	None	None	None	N
M/P	0.9742	likely_pathogenic	0.9798	pathogenic	-0.762	Destabilizing	0.974	D	0.397	neutral	None	None	None	None	N
M/Q	0.4363	ambiguous	0.4589	ambiguous	0.095	Stabilizing	0.974	D	0.313	neutral	None	None	None	None	N
M/R	0.6548	likely_pathogenic	0.6458	pathogenic	0.564	Stabilizing	0.966	D	0.338	neutral	N	0.395477807	None	None	N
M/S	0.5693	likely_pathogenic	0.6131	pathogenic	-0.177	Destabilizing	0.728	D	0.274	neutral	None	None	None	None	N
M/T	0.5644	likely_pathogenic	0.6222	pathogenic	-0.134	Destabilizing	0.801	D	0.294	neutral	N	0.414370212	None	None	N
M/V	0.3658	ambiguous	0.3725	ambiguous	-0.762	Destabilizing	0.454	N	0.282	neutral	N	0.46431903	None	None	N
M/W	0.7956	likely_pathogenic	0.8446	pathogenic	-0.535	Destabilizing	0.998	D	0.335	neutral	None	None	None	None	N
M/Y	0.6649	likely_pathogenic	0.729	pathogenic	-0.489	Destabilizing	0.991	D	0.347	neutral	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.