TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15696	47311;47312;47313	chr2:178618372;178618371;178618370	chr2:179483099;179483098;179483097
N2AB	14055	42388;42389;42390	chr2:178618372;178618371;178618370	chr2:179483099;179483098;179483097
N2A	13128	39607;39608;39609	chr2:178618372;178618371;178618370	chr2:179483099;179483098;179483097
N2B	6631	20116;20117;20118	chr2:178618372;178618371;178618370	chr2:179483099;179483098;179483097
Novex-1	6756	20491;20492;20493	chr2:178618372;178618371;178618370	chr2:179483099;179483098;179483097
Novex-2	6823	20692;20693;20694	chr2:178618372;178618371;178618370	chr2:179483099;179483098;179483097
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-1
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.3015
• 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
R/T	rs2057728993	None	0.998	N	0.693	0.393	0.418344901717	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/T	rs2057728993	None	0.998	N	0.693	0.393	0.418344901717	gnomAD-4.0.0	6.5838E-06	None	None	None	None	N	None	2.41488E-05	0	None	0	0	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
R/A	0.9902	likely_pathogenic	0.9775	pathogenic	-2.147	Highly Destabilizing	0.992	D	0.666	neutral	None	None	None	None	N
R/C	0.7797	likely_pathogenic	0.7007	pathogenic	-2.093	Highly Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
R/D	0.9984	likely_pathogenic	0.9958	pathogenic	-1.468	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
R/E	0.9793	likely_pathogenic	0.9525	pathogenic	-1.21	Destabilizing	0.992	D	0.671	neutral	None	None	None	None	N
R/F	0.9834	likely_pathogenic	0.9537	pathogenic	-1.205	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
R/G	0.9826	likely_pathogenic	0.9591	pathogenic	-2.529	Highly Destabilizing	0.994	D	0.711	prob.delet.	D	0.529494159	None	None	N
R/H	0.6767	likely_pathogenic	0.5718	pathogenic	-1.798	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
R/I	0.9336	likely_pathogenic	0.8602	pathogenic	-1.018	Destabilizing	0.999	D	0.753	deleterious	N	0.477488422	None	None	N
R/K	0.3176	likely_benign	0.3082	benign	-1.171	Destabilizing	0.543	D	0.392	neutral	N	0.428035187	None	None	N
R/L	0.9202	likely_pathogenic	0.8281	pathogenic	-1.018	Destabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	N
R/M	0.9439	likely_pathogenic	0.8832	pathogenic	-1.49	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
R/N	0.9945	likely_pathogenic	0.9869	pathogenic	-1.779	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
R/P	0.9988	likely_pathogenic	0.9968	pathogenic	-1.386	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
R/Q	0.636	likely_pathogenic	0.5273	ambiguous	-1.577	Destabilizing	0.998	D	0.694	prob.neutral	None	None	None	None	N
R/S	0.9938	likely_pathogenic	0.9854	pathogenic	-2.663	Highly Destabilizing	0.989	D	0.688	prob.neutral	N	0.504463995	None	None	N
R/T	0.9806	likely_pathogenic	0.9553	pathogenic	-2.163	Highly Destabilizing	0.998	D	0.693	prob.neutral	N	0.520488735	None	None	N
R/V	0.9466	likely_pathogenic	0.8971	pathogenic	-1.386	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
R/W	0.8546	likely_pathogenic	0.7139	pathogenic	-0.65	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
R/Y	0.933	likely_pathogenic	0.8564	pathogenic	-0.602	Destabilizing	1.0	D	0.747	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.