TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15209	45850;45851;45852	chr2:178620985;178620984;178620983	chr2:179485712;179485711;179485710
N2AB	13568	40927;40928;40929	chr2:178620985;178620984;178620983	chr2:179485712;179485711;179485710
N2A	12641	38146;38147;38148	chr2:178620985;178620984;178620983	chr2:179485712;179485711;179485710
N2B	6144	18655;18656;18657	chr2:178620985;178620984;178620983	chr2:179485712;179485711;179485710
Novex-1	6269	19030;19031;19032	chr2:178620985;178620984;178620983	chr2:179485712;179485711;179485710
Novex-2	6336	19231;19232;19233	chr2:178620985;178620984;178620983	chr2:179485712;179485711;179485710
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-104
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5679
• 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/S	None	None	0.09	N	0.31	0.138	0.151104730317	gnomAD-4.0.0	6.85951E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00367E-07	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	0.5161	ambiguous	0.4872	ambiguous	-0.267	Destabilizing	0.116	N	0.3	neutral	None	None	None	None	N
R/C	0.2946	likely_benign	0.2637	benign	-0.445	Destabilizing	0.981	D	0.346	neutral	None	None	None	None	N
R/D	0.7403	likely_pathogenic	0.7352	pathogenic	-0.025	Destabilizing	0.388	N	0.334	neutral	None	None	None	None	N
R/E	0.375	ambiguous	0.3794	ambiguous	0.094	Stabilizing	0.116	N	0.281	neutral	None	None	None	None	N
R/F	0.7209	likely_pathogenic	0.6817	pathogenic	-0.187	Destabilizing	0.818	D	0.351	neutral	None	None	None	None	N
R/G	0.3823	ambiguous	0.3465	ambiguous	-0.548	Destabilizing	0.324	N	0.335	neutral	N	0.489531362	None	None	N
R/H	0.1203	likely_benign	0.1234	benign	-0.95	Destabilizing	0.818	D	0.352	neutral	None	None	None	None	N
R/I	0.3861	ambiguous	0.3442	ambiguous	0.468	Stabilizing	0.527	D	0.383	neutral	None	None	None	None	N
R/K	0.0923	likely_benign	0.0859	benign	-0.362	Destabilizing	None	N	0.133	neutral	N	0.433536328	None	None	N
R/L	0.3937	ambiguous	0.3613	ambiguous	0.468	Stabilizing	0.241	N	0.34	neutral	None	None	None	None	N
R/M	0.3772	ambiguous	0.3254	benign	-0.1	Destabilizing	0.773	D	0.33	neutral	N	0.441558255	None	None	N
R/N	0.5619	ambiguous	0.5583	ambiguous	-0.145	Destabilizing	0.388	N	0.275	neutral	None	None	None	None	N
R/P	0.9489	likely_pathogenic	0.9354	pathogenic	0.245	Stabilizing	0.818	D	0.357	neutral	None	None	None	None	N
R/Q	0.1088	likely_benign	0.1107	benign	-0.181	Destabilizing	0.241	N	0.341	neutral	None	None	None	None	N
R/S	0.5076	ambiguous	0.4901	ambiguous	-0.646	Destabilizing	0.09	N	0.31	neutral	N	0.444960939	None	None	N
R/T	0.285	likely_benign	0.2656	benign	-0.353	Destabilizing	0.001	N	0.219	neutral	N	0.447361167	None	None	N
R/V	0.4439	ambiguous	0.4349	ambiguous	0.245	Stabilizing	0.241	N	0.361	neutral	None	None	None	None	N
R/W	0.3211	likely_benign	0.269	benign	-0.06	Destabilizing	0.975	D	0.395	neutral	N	0.489531362	None	None	N
R/Y	0.5766	likely_pathogenic	0.5477	ambiguous	0.287	Stabilizing	0.932	D	0.356	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.