TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22086	66481;66482;66483	chr2:178582113;178582112;178582111	chr2:179446840;179446839;179446838
N2AB	20445	61558;61559;61560	chr2:178582113;178582112;178582111	chr2:179446840;179446839;179446838
N2A	19518	58777;58778;58779	chr2:178582113;178582112;178582111	chr2:179446840;179446839;179446838
N2B	13021	39286;39287;39288	chr2:178582113;178582112;178582111	chr2:179446840;179446839;179446838
Novex-1	13146	39661;39662;39663	chr2:178582113;178582112;178582111	chr2:179446840;179446839;179446838
Novex-2	13213	39862;39863;39864	chr2:178582113;178582112;178582111	chr2:179446840;179446839;179446838
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-48
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6418
• 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
P/A	None	None	0.489	N	0.553	0.226	0.231873229951	gnomAD-4.0.0	6.84592E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99641E-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
P/A	0.1059	likely_benign	0.0771	benign	-0.54	Destabilizing	0.489	N	0.553	neutral	N	0.47218216	None	None	N
P/C	0.7365	likely_pathogenic	0.5595	ambiguous	-0.555	Destabilizing	0.998	D	0.696	prob.neutral	None	None	None	None	N
P/D	0.6457	likely_pathogenic	0.4189	ambiguous	-0.313	Destabilizing	0.956	D	0.57	neutral	None	None	None	None	N
P/E	0.4076	ambiguous	0.2444	benign	-0.434	Destabilizing	0.956	D	0.579	neutral	None	None	None	None	N
P/F	0.7456	likely_pathogenic	0.5796	pathogenic	-0.812	Destabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
P/G	0.5264	ambiguous	0.3547	ambiguous	-0.679	Destabilizing	0.754	D	0.591	neutral	None	None	None	None	N
P/H	0.4004	ambiguous	0.2557	benign	-0.284	Destabilizing	0.997	D	0.657	neutral	N	0.507353939	None	None	N
P/I	0.4055	ambiguous	0.2962	benign	-0.327	Destabilizing	0.956	D	0.717	prob.delet.	None	None	None	None	N
P/K	0.5012	ambiguous	0.3204	benign	-0.382	Destabilizing	0.956	D	0.575	neutral	None	None	None	None	N
P/L	0.2042	likely_benign	0.1456	benign	-0.327	Destabilizing	0.822	D	0.61	neutral	N	0.511076922	None	None	N
P/M	0.3814	ambiguous	0.2782	benign	-0.226	Destabilizing	0.998	D	0.659	neutral	None	None	None	None	N
P/N	0.4788	ambiguous	0.308	benign	-0.095	Destabilizing	0.956	D	0.629	neutral	None	None	None	None	N
P/Q	0.2614	likely_benign	0.1623	benign	-0.375	Destabilizing	0.956	D	0.637	neutral	None	None	None	None	N
P/R	0.4306	ambiguous	0.256	benign	0.153	Stabilizing	0.942	D	0.689	prob.neutral	N	0.486780922	None	None	N
P/S	0.2128	likely_benign	0.13	benign	-0.476	Destabilizing	0.125	N	0.34	neutral	N	0.469055061	None	None	N
P/T	0.1397	likely_benign	0.0974	benign	-0.495	Destabilizing	0.058	N	0.273	neutral	N	0.475068995	None	None	N
P/V	0.2465	likely_benign	0.1842	benign	-0.363	Destabilizing	0.86	D	0.579	neutral	None	None	None	None	N
P/W	0.8862	likely_pathogenic	0.7628	pathogenic	-0.88	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
P/Y	0.7181	likely_pathogenic	0.5349	ambiguous	-0.567	Destabilizing	0.993	D	0.696	prob.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.