TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17342	52249;52250;52251	chr2:178609286;178609285;178609284	chr2:179474013;179474012;179474011
N2AB	15701	47326;47327;47328	chr2:178609286;178609285;178609284	chr2:179474013;179474012;179474011
N2A	14774	44545;44546;44547	chr2:178609286;178609285;178609284	chr2:179474013;179474012;179474011
N2B	8277	25054;25055;25056	chr2:178609286;178609285;178609284	chr2:179474013;179474012;179474011
Novex-1	8402	25429;25430;25431	chr2:178609286;178609285;178609284	chr2:179474013;179474012;179474011
Novex-2	8469	25630;25631;25632	chr2:178609286;178609285;178609284	chr2:179474013;179474012;179474011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-112
• Domain position: 92
• Structural Position: 148
• Q(SASA): 0.4929
• 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/L	None	None	None	N	0.242	0.07	0.290222751274	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
P/A	0.075	likely_benign	0.0889	benign	-0.869	Destabilizing	None	N	0.103	neutral	N	0.408606528	None	None	N
P/C	0.4357	ambiguous	0.4968	ambiguous	-0.543	Destabilizing	0.864	D	0.279	neutral	None	None	None	None	N
P/D	0.3101	likely_benign	0.3733	ambiguous	-0.892	Destabilizing	0.038	N	0.251	neutral	None	None	None	None	N
P/E	0.2032	likely_benign	0.2395	benign	-0.978	Destabilizing	None	N	0.209	neutral	None	None	None	None	N
P/F	0.4702	ambiguous	0.5338	ambiguous	-0.927	Destabilizing	0.12	N	0.341	neutral	None	None	None	None	N
P/G	0.1946	likely_benign	0.2422	benign	-1.057	Destabilizing	0.016	N	0.217	neutral	None	None	None	None	N
P/H	0.2057	likely_benign	0.2463	benign	-0.559	Destabilizing	None	N	0.202	neutral	N	0.460998218	None	None	N
P/I	0.2718	likely_benign	0.3257	benign	-0.498	Destabilizing	0.038	N	0.383	neutral	None	None	None	None	N
P/K	0.2414	likely_benign	0.2909	benign	-0.806	Destabilizing	0.016	N	0.227	neutral	None	None	None	None	N
P/L	0.1282	likely_benign	0.1472	benign	-0.498	Destabilizing	None	N	0.242	neutral	N	0.461171576	None	None	N
P/M	0.2675	likely_benign	0.3215	benign	-0.383	Destabilizing	0.12	N	0.285	neutral	None	None	None	None	N
P/N	0.2535	likely_benign	0.3203	benign	-0.491	Destabilizing	0.072	N	0.307	neutral	None	None	None	None	N
P/Q	0.1595	likely_benign	0.1865	benign	-0.753	Destabilizing	0.038	N	0.341	neutral	None	None	None	None	N
P/R	0.1957	likely_benign	0.2208	benign	-0.177	Destabilizing	None	N	0.157	neutral	N	0.441623024	None	None	N
P/S	0.1159	likely_benign	0.1392	benign	-0.828	Destabilizing	0.012	N	0.263	neutral	N	0.384534803	None	None	N
P/T	0.098	likely_benign	0.1191	benign	-0.82	Destabilizing	0.001	N	0.204	neutral	N	0.400237761	None	None	N
P/V	0.1712	likely_benign	0.2101	benign	-0.587	Destabilizing	0.016	N	0.227	neutral	None	None	None	None	N
P/W	0.6039	likely_pathogenic	0.6736	pathogenic	-1.036	Destabilizing	0.864	D	0.309	neutral	None	None	None	None	N
P/Y	0.4183	ambiguous	0.4866	ambiguous	-0.763	Destabilizing	0.214	N	0.367	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.