TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17649	53170;53171;53172	chr2:178607842;178607841;178607840	chr2:179472569;179472568;179472567
N2AB	16008	48247;48248;48249	chr2:178607842;178607841;178607840	chr2:179472569;179472568;179472567
N2A	15081	45466;45467;45468	chr2:178607842;178607841;178607840	chr2:179472569;179472568;179472567
N2B	8584	25975;25976;25977	chr2:178607842;178607841;178607840	chr2:179472569;179472568;179472567
Novex-1	8709	26350;26351;26352	chr2:178607842;178607841;178607840	chr2:179472569;179472568;179472567
Novex-2	8776	26551;26552;26553	chr2:178607842;178607841;178607840	chr2:179472569;179472568;179472567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-16
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.7376
• Predicted PPI site: I

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
A/P	rs2055287229	None	0.741	N	0.368	0.161	0.225902525712	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	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
A/C	0.3402	ambiguous	0.3483	ambiguous	-0.816	Destabilizing	0.003	N	0.322	neutral	None	None	None	None	I
A/D	0.1911	likely_benign	0.1576	benign	-0.514	Destabilizing	0.484	N	0.517	neutral	N	0.465628539	None	None	I
A/E	0.1679	likely_benign	0.1588	benign	-0.673	Destabilizing	0.555	D	0.382	neutral	None	None	None	None	I
A/F	0.2246	likely_benign	0.2112	benign	-0.912	Destabilizing	0.235	N	0.517	neutral	None	None	None	None	I
A/G	0.115	likely_benign	0.1167	benign	-0.233	Destabilizing	0.211	N	0.299	neutral	N	0.509509815	None	None	I
A/H	0.3392	likely_benign	0.3146	benign	-0.223	Destabilizing	0.935	D	0.497	neutral	None	None	None	None	I
A/I	0.1328	likely_benign	0.1259	benign	-0.388	Destabilizing	0.001	N	0.297	neutral	None	None	None	None	I
A/K	0.2678	likely_benign	0.2625	benign	-0.529	Destabilizing	0.555	D	0.371	neutral	None	None	None	None	I
A/L	0.1059	likely_benign	0.1059	benign	-0.388	Destabilizing	0.001	N	0.255	neutral	None	None	None	None	I
A/M	0.1479	likely_benign	0.1392	benign	-0.447	Destabilizing	0.235	N	0.358	neutral	None	None	None	None	I
A/N	0.1878	likely_benign	0.1593	benign	-0.255	Destabilizing	0.791	D	0.509	neutral	None	None	None	None	I
A/P	0.2292	likely_benign	0.2315	benign	-0.304	Destabilizing	0.741	D	0.368	neutral	N	0.495298085	None	None	I
A/Q	0.2302	likely_benign	0.2283	benign	-0.543	Destabilizing	0.791	D	0.362	neutral	None	None	None	None	I
A/R	0.2505	likely_benign	0.2499	benign	-0.062	Destabilizing	0.555	D	0.362	neutral	None	None	None	None	I
A/S	0.0941	likely_benign	0.0877	benign	-0.436	Destabilizing	0.117	N	0.321	neutral	N	0.46293495	None	None	I
A/T	0.0837	likely_benign	0.0791	benign	-0.521	Destabilizing	0.062	N	0.29	neutral	N	0.513323698	None	None	I
A/V	0.0819	likely_benign	0.0833	benign	-0.304	Destabilizing	None	N	0.102	neutral	N	0.498471676	None	None	I
A/W	0.5688	likely_pathogenic	0.5559	ambiguous	-1.014	Destabilizing	0.935	D	0.611	neutral	None	None	None	None	I
A/Y	0.353	ambiguous	0.3117	benign	-0.683	Destabilizing	0.555	D	0.509	neutral	None	None	None	None	I

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.