TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1122	3589;3590;3591	chr2:178782228;178782227;178782226	chr2:179646955;179646954;179646953
N2AB	1122	3589;3590;3591	chr2:178782228;178782227;178782226	chr2:179646955;179646954;179646953
N2A	1122	3589;3590;3591	chr2:178782228;178782227;178782226	chr2:179646955;179646954;179646953
N2B	1076	3451;3452;3453	chr2:178782228;178782227;178782226	chr2:179646955;179646954;179646953
Novex-1	1076	3451;3452;3453	chr2:178782228;178782227;178782226	chr2:179646955;179646954;179646953
Novex-2	1076	3451;3452;3453	chr2:178782228;178782227;178782226	chr2:179646955;179646954;179646953
Novex-3	1122	3589;3590;3591	chr2:178782228;178782227;178782226	chr2:179646955;179646954;179646953

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-4
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1968
• 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
L/P	rs1189198137	-1.423	1.0	D	0.863	0.838	0.905625399933	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	5.45E-05	None	0	None	0	0	0
L/P	rs1189198137	-1.423	1.0	D	0.863	0.838	0.905625399933	gnomAD-4.0.0	1.59054E-06	None	None	None	None	N	None	0	0	None	0	2.77346E-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
L/A	0.977	likely_pathogenic	0.9693	pathogenic	-2.239	Highly Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
L/C	0.9885	likely_pathogenic	0.9805	pathogenic	-1.488	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-2.132	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.9965	pathogenic	-1.919	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/F	0.903	likely_pathogenic	0.8676	pathogenic	-1.321	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
L/G	0.998	likely_pathogenic	0.9973	pathogenic	-2.751	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/H	0.9959	likely_pathogenic	0.9933	pathogenic	-1.998	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/I	0.2973	likely_benign	0.2434	benign	-0.777	Destabilizing	0.999	D	0.527	neutral	N	0.468719911	None	None	N
L/K	0.9946	likely_pathogenic	0.9919	pathogenic	-1.674	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/M	0.5533	ambiguous	0.4839	ambiguous	-0.712	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
L/N	0.9983	likely_pathogenic	0.9975	pathogenic	-1.967	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/P	0.9979	likely_pathogenic	0.9971	pathogenic	-1.244	Destabilizing	1.0	D	0.863	deleterious	D	0.655461329	None	None	N
L/Q	0.99	likely_pathogenic	0.9851	pathogenic	-1.831	Destabilizing	1.0	D	0.846	deleterious	D	0.655900012	None	None	N
L/R	0.9903	likely_pathogenic	0.9855	pathogenic	-1.432	Destabilizing	1.0	D	0.851	deleterious	D	0.671397692	None	None	N
L/S	0.9972	likely_pathogenic	0.9959	pathogenic	-2.681	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/T	0.9864	likely_pathogenic	0.9819	pathogenic	-2.31	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
L/V	0.3642	ambiguous	0.3031	benign	-1.244	Destabilizing	0.999	D	0.514	neutral	N	0.514658416	None	None	N
L/W	0.9922	likely_pathogenic	0.9881	pathogenic	-1.577	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/Y	0.9938	likely_pathogenic	0.9897	pathogenic	-1.285	Destabilizing	1.0	D	0.828	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.