TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22381	67366;67367;67368	chr2:178580146;178580145;178580144	chr2:179444873;179444872;179444871
N2AB	20740	62443;62444;62445	chr2:178580146;178580145;178580144	chr2:179444873;179444872;179444871
N2A	19813	59662;59663;59664	chr2:178580146;178580145;178580144	chr2:179444873;179444872;179444871
N2B	13316	40171;40172;40173	chr2:178580146;178580145;178580144	chr2:179444873;179444872;179444871
Novex-1	13441	40546;40547;40548	chr2:178580146;178580145;178580144	chr2:179444873;179444872;179444871
Novex-2	13508	40747;40748;40749	chr2:178580146;178580145;178580144	chr2:179444873;179444872;179444871
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-50
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2777
• 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
D/H	None	None	1.0	N	0.659	0.583	0.446410834509	gnomAD-4.0.0	3.60099E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.93751E-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
D/A	0.93	likely_pathogenic	0.9423	pathogenic	-0.562	Destabilizing	1.0	D	0.721	prob.delet.	N	0.503262108	None	None	I
D/C	0.9852	likely_pathogenic	0.9878	pathogenic	-0.121	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
D/E	0.8718	likely_pathogenic	0.872	pathogenic	-0.643	Destabilizing	1.0	D	0.445	neutral	N	0.48990434	None	None	I
D/F	0.9904	likely_pathogenic	0.991	pathogenic	-0.499	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
D/G	0.9163	likely_pathogenic	0.9333	pathogenic	-0.854	Destabilizing	1.0	D	0.703	prob.neutral	N	0.518772697	None	None	I
D/H	0.9547	likely_pathogenic	0.9633	pathogenic	-0.857	Destabilizing	1.0	D	0.659	neutral	N	0.516201803	None	None	I
D/I	0.984	likely_pathogenic	0.9863	pathogenic	0.187	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
D/K	0.9865	likely_pathogenic	0.9892	pathogenic	-0.217	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
D/L	0.9752	likely_pathogenic	0.9776	pathogenic	0.187	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
D/M	0.9937	likely_pathogenic	0.9941	pathogenic	0.635	Stabilizing	1.0	D	0.64	neutral	None	None	None	None	I
D/N	0.4221	ambiguous	0.433	ambiguous	-0.543	Destabilizing	1.0	D	0.696	prob.neutral	N	0.470105018	None	None	I
D/P	0.9896	likely_pathogenic	0.9898	pathogenic	-0.039	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
D/Q	0.9776	likely_pathogenic	0.9814	pathogenic	-0.453	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
D/R	0.981	likely_pathogenic	0.9848	pathogenic	-0.2	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/S	0.7091	likely_pathogenic	0.7413	pathogenic	-0.734	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
D/T	0.8968	likely_pathogenic	0.9111	pathogenic	-0.498	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
D/V	0.959	likely_pathogenic	0.9644	pathogenic	-0.039	Destabilizing	1.0	D	0.699	prob.neutral	N	0.521619853	None	None	I
D/W	0.9975	likely_pathogenic	0.9978	pathogenic	-0.384	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
D/Y	0.9248	likely_pathogenic	0.9383	pathogenic	-0.278	Destabilizing	1.0	D	0.629	neutral	D	0.536712368	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.