TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20883	62872;62873;62874	chr2:178589078;178589077;178589076	chr2:179453805;179453804;179453803
N2AB	19242	57949;57950;57951	chr2:178589078;178589077;178589076	chr2:179453805;179453804;179453803
N2A	18315	55168;55169;55170	chr2:178589078;178589077;178589076	chr2:179453805;179453804;179453803
N2B	11818	35677;35678;35679	chr2:178589078;178589077;178589076	chr2:179453805;179453804;179453803
Novex-1	11943	36052;36053;36054	chr2:178589078;178589077;178589076	chr2:179453805;179453804;179453803
Novex-2	12010	36253;36254;36255	chr2:178589078;178589077;178589076	chr2:179453805;179453804;179453803
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-39
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1184
• 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	N	0.219	0.046	0.220303561663	gnomAD-4.0.0	6.86056E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99596E-07	0	0
V/L	None	None	None	N	0.257	0.025	0.0482279557977	gnomAD-4.0.0	6.86056E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99596E-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
V/A	0.6597	likely_pathogenic	0.5916	pathogenic	-1.994	Destabilizing	0.052	N	0.638	neutral	N	0.487439259	None	None	N
V/C	0.9026	likely_pathogenic	0.8707	pathogenic	-1.603	Destabilizing	0.935	D	0.77	deleterious	None	None	None	None	N
V/D	0.9966	likely_pathogenic	0.9953	pathogenic	-2.924	Highly Destabilizing	0.484	N	0.852	deleterious	N	0.517913777	None	None	N
V/E	0.9906	likely_pathogenic	0.9879	pathogenic	-2.603	Highly Destabilizing	0.555	D	0.798	deleterious	None	None	None	None	N
V/F	0.5098	ambiguous	0.4569	ambiguous	-1.138	Destabilizing	0.001	N	0.621	neutral	N	0.484552423	None	None	N
V/G	0.8989	likely_pathogenic	0.8563	pathogenic	-2.628	Highly Destabilizing	0.484	N	0.809	deleterious	N	0.517660288	None	None	N
V/H	0.9944	likely_pathogenic	0.9926	pathogenic	-2.695	Highly Destabilizing	0.935	D	0.866	deleterious	None	None	None	None	N
V/I	0.0636	likely_benign	0.0673	benign	-0.167	Destabilizing	None	N	0.219	neutral	N	0.50212527	None	None	N
V/K	0.9914	likely_pathogenic	0.99	pathogenic	-1.619	Destabilizing	0.555	D	0.778	deleterious	None	None	None	None	N
V/L	0.1471	likely_benign	0.1202	benign	-0.167	Destabilizing	None	N	0.257	neutral	N	0.394485224	None	None	N
V/M	0.3249	likely_benign	0.2951	benign	-0.451	Destabilizing	0.235	N	0.663	neutral	None	None	None	None	N
V/N	0.9859	likely_pathogenic	0.9813	pathogenic	-2.272	Highly Destabilizing	0.791	D	0.857	deleterious	None	None	None	None	N
V/P	0.9799	likely_pathogenic	0.9733	pathogenic	-0.753	Destabilizing	0.791	D	0.831	deleterious	None	None	None	None	N
V/Q	0.9868	likely_pathogenic	0.9829	pathogenic	-1.893	Destabilizing	0.791	D	0.837	deleterious	None	None	None	None	N
V/R	0.9847	likely_pathogenic	0.9824	pathogenic	-1.827	Destabilizing	0.555	D	0.855	deleterious	None	None	None	None	N
V/S	0.9447	likely_pathogenic	0.928	pathogenic	-2.835	Highly Destabilizing	0.555	D	0.765	deleterious	None	None	None	None	N
V/T	0.862	likely_pathogenic	0.8358	pathogenic	-2.339	Highly Destabilizing	0.149	N	0.655	neutral	None	None	None	None	N
V/W	0.9921	likely_pathogenic	0.9881	pathogenic	-1.765	Destabilizing	0.935	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9607	likely_pathogenic	0.9528	pathogenic	-1.339	Destabilizing	0.235	N	0.723	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.