TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10042	30349;30350;30351	chr2:178704246;178704245;178704244	chr2:179568973;179568972;179568971
N2AB	9725	29398;29399;29400	chr2:178704246;178704245;178704244	chr2:179568973;179568972;179568971
N2A	8798	26617;26618;26619	chr2:178704246;178704245;178704244	chr2:179568973;179568972;179568971
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-85
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.2402
• 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
V/F	None	None	0.983	None	0.73	0.319	0.674832526739	gnomAD-4.0.0	6.84139E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99397E-07	0	0
V/L	None	None	0.63	None	0.403	0.211	0.480801007081	gnomAD-4.0.0	6.84139E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	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
V/A	0.4125	ambiguous	0.512	ambiguous	-1.703	Destabilizing	0.025	N	0.395	neutral	None	None	None	None	N
V/C	0.9209	likely_pathogenic	0.9528	pathogenic	-0.949	Destabilizing	0.997	D	0.69	prob.neutral	None	None	None	None	N
V/D	0.6359	likely_pathogenic	0.711	pathogenic	-2.315	Highly Destabilizing	0.983	D	0.787	deleterious	None	None	None	None	N
V/E	0.4123	ambiguous	0.4644	ambiguous	-2.302	Highly Destabilizing	0.975	D	0.737	prob.delet.	None	None	None	None	N
V/F	0.2921	likely_benign	0.3703	ambiguous	-1.319	Destabilizing	0.983	D	0.73	prob.delet.	None	None	None	None	N
V/G	0.4938	ambiguous	0.6098	pathogenic	-2.028	Highly Destabilizing	0.935	D	0.723	prob.delet.	None	None	None	None	N
V/H	0.7805	likely_pathogenic	0.8501	pathogenic	-1.769	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
V/I	0.0801	likely_benign	0.0835	benign	-0.877	Destabilizing	0.099	N	0.353	neutral	None	None	None	None	N
V/K	0.5582	ambiguous	0.6286	pathogenic	-1.494	Destabilizing	0.975	D	0.739	prob.delet.	None	None	None	None	N
V/L	0.3381	likely_benign	0.4164	ambiguous	-0.877	Destabilizing	0.63	D	0.403	neutral	None	None	None	None	N
V/M	0.2119	likely_benign	0.2708	benign	-0.514	Destabilizing	0.987	D	0.581	neutral	None	None	None	None	N
V/N	0.4628	ambiguous	0.5693	pathogenic	-1.313	Destabilizing	0.987	D	0.79	deleterious	None	None	None	None	N
V/P	0.9893	likely_pathogenic	0.9942	pathogenic	-1.122	Destabilizing	0.987	D	0.75	deleterious	None	None	None	None	N
V/Q	0.4944	ambiguous	0.5675	pathogenic	-1.486	Destabilizing	0.987	D	0.759	deleterious	None	None	None	None	N
V/R	0.5372	ambiguous	0.6025	pathogenic	-0.961	Destabilizing	0.987	D	0.791	deleterious	None	None	None	None	N
V/S	0.4462	ambiguous	0.5548	ambiguous	-1.692	Destabilizing	0.95	D	0.683	prob.neutral	None	None	None	None	N
V/T	0.3081	likely_benign	0.3859	ambiguous	-1.594	Destabilizing	0.916	D	0.497	neutral	None	None	None	None	N
V/W	0.9011	likely_pathogenic	0.9349	pathogenic	-1.659	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
V/Y	0.6987	likely_pathogenic	0.7762	pathogenic	-1.387	Destabilizing	0.996	D	0.732	prob.delet.	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.