TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9960	30103;30104;30105	chr2:178704594;178704593;178704592	chr2:179569321;179569320;179569319
N2AB	9643	29152;29153;29154	chr2:178704594;178704593;178704592	chr2:179569321;179569320;179569319
N2A	8716	26371;26372;26373	chr2:178704594;178704593;178704592	chr2:179569321;179569320;179569319
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-84
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.0984
• 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/I	None	None	None	None	0.245	0.055	0.247322355667	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
V/A	0.9433	likely_pathogenic	0.9541	pathogenic	-2.499	Highly Destabilizing	0.104	N	0.617	neutral	None	None	None	None	N
V/C	0.9724	likely_pathogenic	0.9799	pathogenic	-2.125	Highly Destabilizing	0.968	D	0.769	deleterious	None	None	None	None	N
V/D	0.9977	likely_pathogenic	0.9974	pathogenic	-3.552	Highly Destabilizing	0.667	D	0.873	deleterious	None	None	None	None	N
V/E	0.9891	likely_pathogenic	0.9894	pathogenic	-3.235	Highly Destabilizing	0.726	D	0.85	deleterious	None	None	None	None	N
V/F	0.8339	likely_pathogenic	0.8569	pathogenic	-1.422	Destabilizing	0.497	N	0.771	deleterious	None	None	None	None	N
V/G	0.9679	likely_pathogenic	0.9669	pathogenic	-3.116	Highly Destabilizing	0.667	D	0.859	deleterious	None	None	None	None	N
V/H	0.9965	likely_pathogenic	0.9966	pathogenic	-3.031	Highly Destabilizing	0.968	D	0.865	deleterious	None	None	None	None	N
V/I	0.0823	likely_benign	0.0921	benign	-0.7	Destabilizing	None	N	0.245	neutral	None	None	None	None	N
V/K	0.9886	likely_pathogenic	0.9889	pathogenic	-2.095	Highly Destabilizing	0.726	D	0.848	deleterious	None	None	None	None	N
V/L	0.5353	ambiguous	0.6302	pathogenic	-0.7	Destabilizing	0.009	N	0.374	neutral	None	None	None	None	N
V/M	0.6515	likely_pathogenic	0.717	pathogenic	-0.992	Destabilizing	0.567	D	0.669	neutral	None	None	None	None	N
V/N	0.9909	likely_pathogenic	0.9914	pathogenic	-2.785	Highly Destabilizing	0.89	D	0.877	deleterious	None	None	None	None	N
V/P	0.9971	likely_pathogenic	0.9975	pathogenic	-1.282	Destabilizing	0.89	D	0.85	deleterious	None	None	None	None	N
V/Q	0.9888	likely_pathogenic	0.9896	pathogenic	-2.427	Highly Destabilizing	0.89	D	0.878	deleterious	None	None	None	None	N
V/R	0.9849	likely_pathogenic	0.9836	pathogenic	-2.151	Highly Destabilizing	0.726	D	0.879	deleterious	None	None	None	None	N
V/S	0.9847	likely_pathogenic	0.9859	pathogenic	-3.314	Highly Destabilizing	0.726	D	0.821	deleterious	None	None	None	None	N
V/T	0.9646	likely_pathogenic	0.9708	pathogenic	-2.837	Highly Destabilizing	0.272	N	0.654	neutral	None	None	None	None	N
V/W	0.9963	likely_pathogenic	0.9968	pathogenic	-2.05	Highly Destabilizing	0.968	D	0.861	deleterious	None	None	None	None	N
V/Y	0.9837	likely_pathogenic	0.9846	pathogenic	-1.743	Destabilizing	0.726	D	0.77	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.