TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7749	23470;23471;23472	chr2:178720517;178720516;178720515	chr2:179585244;179585243;179585242
N2AB	7432	22519;22520;22521	chr2:178720517;178720516;178720515	chr2:179585244;179585243;179585242
N2A	6505	19738;19739;19740	chr2:178720517;178720516;178720515	chr2:179585244;179585243;179585242
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-62
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.6115
• 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
K/T	None	None	0.883	N	0.333	0.328	0.386721274199	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.8638	likely_pathogenic	0.8842	pathogenic	-0.609	Destabilizing	0.932	D	0.321	neutral	None	None	None	None	N
K/C	0.9158	likely_pathogenic	0.9224	pathogenic	-0.575	Destabilizing	1.0	D	0.341	neutral	None	None	None	None	N
K/D	0.9583	likely_pathogenic	0.966	pathogenic	-0.088	Destabilizing	0.985	D	0.359	neutral	None	None	None	None	N
K/E	0.7205	likely_pathogenic	0.755	pathogenic	0.023	Stabilizing	0.938	D	0.323	neutral	N	0.520957039	None	None	N
K/F	0.9585	likely_pathogenic	0.9626	pathogenic	-0.309	Destabilizing	0.995	D	0.354	neutral	None	None	None	None	N
K/G	0.9296	likely_pathogenic	0.9428	pathogenic	-0.981	Destabilizing	0.08	N	0.209	neutral	None	None	None	None	N
K/H	0.5023	ambiguous	0.5134	ambiguous	-1.343	Destabilizing	0.998	D	0.343	neutral	None	None	None	None	N
K/I	0.7268	likely_pathogenic	0.7391	pathogenic	0.357	Stabilizing	0.425	N	0.349	neutral	N	0.48596318	None	None	N
K/L	0.7386	likely_pathogenic	0.7503	pathogenic	0.357	Stabilizing	0.494	N	0.357	neutral	None	None	None	None	N
K/M	0.6237	likely_pathogenic	0.6354	pathogenic	0.312	Stabilizing	0.983	D	0.342	neutral	None	None	None	None	N
K/N	0.8779	likely_pathogenic	0.8918	pathogenic	-0.437	Destabilizing	0.98	D	0.295	neutral	N	0.491328324	None	None	N
K/P	0.9914	likely_pathogenic	0.9929	pathogenic	0.065	Stabilizing	0.998	D	0.352	neutral	None	None	None	None	N
K/Q	0.3026	likely_benign	0.3173	benign	-0.522	Destabilizing	0.858	D	0.355	neutral	N	0.457292349	None	None	N
K/R	0.0929	likely_benign	0.095	benign	-0.618	Destabilizing	0.028	N	0.176	neutral	N	0.468258704	None	None	N
K/S	0.8589	likely_pathogenic	0.8762	pathogenic	-1.135	Destabilizing	0.721	D	0.126	neutral	None	None	None	None	N
K/T	0.5814	likely_pathogenic	0.609	pathogenic	-0.811	Destabilizing	0.883	D	0.333	neutral	N	0.512030911	None	None	N
K/V	0.7169	likely_pathogenic	0.7254	pathogenic	0.065	Stabilizing	0.033	N	0.278	neutral	None	None	None	None	N
K/W	0.9261	likely_pathogenic	0.9305	pathogenic	-0.168	Destabilizing	1.0	D	0.382	neutral	None	None	None	None	N
K/Y	0.8895	likely_pathogenic	0.8949	pathogenic	0.127	Stabilizing	0.985	D	0.335	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.