TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16489	49690;49691;49692	chr2:178613818;178613817;178613816	chr2:179478545;179478544;179478543
N2AB	14848	44767;44768;44769	chr2:178613818;178613817;178613816	chr2:179478545;179478544;179478543
N2A	13921	41986;41987;41988	chr2:178613818;178613817;178613816	chr2:179478545;179478544;179478543
N2B	7424	22495;22496;22497	chr2:178613818;178613817;178613816	chr2:179478545;179478544;179478543
Novex-1	7549	22870;22871;22872	chr2:178613818;178613817;178613816	chr2:179478545;179478544;179478543
Novex-2	7616	23071;23072;23073	chr2:178613818;178613817;178613816	chr2:179478545;179478544;179478543
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: Fn3-7
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2183
• 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/I	rs878912537	None	0.991	N	0.778	0.339	0.441636318388	gnomAD-4.0.0	3.60099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93752E-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
R/A	0.9392	likely_pathogenic	0.9335	pathogenic	-2.236	Highly Destabilizing	0.953	D	0.691	prob.neutral	None	None	None	None	N
R/C	0.398	ambiguous	0.3647	ambiguous	-2.235	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
R/D	0.9941	likely_pathogenic	0.9935	pathogenic	-1.702	Destabilizing	0.986	D	0.742	deleterious	None	None	None	None	N
R/E	0.9364	likely_pathogenic	0.9299	pathogenic	-1.436	Destabilizing	0.91	D	0.655	neutral	None	None	None	None	N
R/F	0.8619	likely_pathogenic	0.8608	pathogenic	-1.277	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
R/G	0.9196	likely_pathogenic	0.9171	pathogenic	-2.622	Highly Destabilizing	0.939	D	0.735	prob.delet.	N	0.469108851	None	None	N
R/H	0.3671	ambiguous	0.325	benign	-1.982	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
R/I	0.7654	likely_pathogenic	0.7739	pathogenic	-1.09	Destabilizing	0.991	D	0.778	deleterious	N	0.471434387	None	None	N
R/K	0.2132	likely_benign	0.1802	benign	-1.36	Destabilizing	0.046	N	0.348	neutral	N	0.430984709	None	None	N
R/L	0.739	likely_pathogenic	0.7025	pathogenic	-1.09	Destabilizing	0.953	D	0.735	prob.delet.	None	None	None	None	N
R/M	0.6962	likely_pathogenic	0.6496	pathogenic	-1.557	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
R/N	0.9742	likely_pathogenic	0.9705	pathogenic	-2.045	Highly Destabilizing	0.986	D	0.671	neutral	None	None	None	None	N
R/P	0.9983	likely_pathogenic	0.9983	pathogenic	-1.464	Destabilizing	0.993	D	0.752	deleterious	None	None	None	None	N
R/Q	0.354	ambiguous	0.3213	benign	-1.762	Destabilizing	0.986	D	0.673	neutral	None	None	None	None	N
R/S	0.9626	likely_pathogenic	0.9599	pathogenic	-2.862	Highly Destabilizing	0.939	D	0.706	prob.neutral	N	0.473328214	None	None	N
R/T	0.9207	likely_pathogenic	0.905	pathogenic	-2.35	Highly Destabilizing	0.982	D	0.723	prob.delet.	N	0.512566976	None	None	N
R/V	0.8173	likely_pathogenic	0.8152	pathogenic	-1.464	Destabilizing	0.993	D	0.766	deleterious	None	None	None	None	N
R/W	0.5955	likely_pathogenic	0.6138	pathogenic	-0.761	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
R/Y	0.679	likely_pathogenic	0.6631	pathogenic	-0.711	Destabilizing	0.998	D	0.764	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.