TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2396	7411;7412;7413	chr2:178773982;178773981;178773980	chr2:179638709;179638708;179638707
N2AB	2396	7411;7412;7413	chr2:178773982;178773981;178773980	chr2:179638709;179638708;179638707
N2A	2396	7411;7412;7413	chr2:178773982;178773981;178773980	chr2:179638709;179638708;179638707
N2B	2350	7273;7274;7275	chr2:178773982;178773981;178773980	chr2:179638709;179638708;179638707
Novex-1	2350	7273;7274;7275	chr2:178773982;178773981;178773980	chr2:179638709;179638708;179638707
Novex-2	2350	7273;7274;7275	chr2:178773982;178773981;178773980	chr2:179638709;179638708;179638707
Novex-3	2396	7411;7412;7413	chr2:178773982;178773981;178773980	chr2:179638709;179638708;179638707

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-13
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.8162
• 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
Q/L	None	None	0.175	N	0.381	0.209	0.40722173914	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
Q/A	0.1439	likely_benign	0.1425	benign	-0.018	Destabilizing	0.025	N	0.291	neutral	None	None	None	None	N
Q/C	0.3824	ambiguous	0.366	ambiguous	-0.096	Destabilizing	0.958	D	0.336	neutral	None	None	None	None	N
Q/D	0.2685	likely_benign	0.2596	benign	0.029	Stabilizing	0.055	N	0.35	neutral	None	None	None	None	N
Q/E	0.0827	likely_benign	0.0849	benign	0.007	Stabilizing	None	N	0.218	neutral	N	0.502009163	None	None	N
Q/F	0.3678	ambiguous	0.3426	ambiguous	-0.336	Destabilizing	0.859	D	0.356	neutral	None	None	None	None	N
Q/G	0.2075	likely_benign	0.205	benign	-0.17	Destabilizing	0.104	N	0.357	neutral	None	None	None	None	N
Q/H	0.1171	likely_benign	0.1132	benign	0.091	Stabilizing	0.602	D	0.393	neutral	N	0.511413645	None	None	N
Q/I	0.1766	likely_benign	0.173	benign	0.289	Stabilizing	0.667	D	0.367	neutral	None	None	None	None	N
Q/K	0.0726	likely_benign	0.0726	benign	0.09	Stabilizing	0.042	N	0.357	neutral	N	0.489547372	None	None	N
Q/L	0.0773	likely_benign	0.0782	benign	0.289	Stabilizing	0.175	N	0.381	neutral	N	0.511413645	None	None	N
Q/M	0.2158	likely_benign	0.2114	benign	0.143	Stabilizing	0.859	D	0.397	neutral	None	None	None	None	N
Q/N	0.1901	likely_benign	0.1794	benign	-0.34	Destabilizing	0.22	N	0.321	neutral	None	None	None	None	N
Q/P	0.1095	likely_benign	0.1143	benign	0.213	Stabilizing	0.001	N	0.183	neutral	N	0.50930727	None	None	N
Q/R	0.0892	likely_benign	0.0888	benign	0.273	Stabilizing	0.175	N	0.342	neutral	N	0.500244014	None	None	N
Q/S	0.16	likely_benign	0.1519	benign	-0.291	Destabilizing	0.005	N	0.177	neutral	None	None	None	None	N
Q/T	0.13	likely_benign	0.1262	benign	-0.17	Destabilizing	0.055	N	0.361	neutral	None	None	None	None	N
Q/V	0.1339	likely_benign	0.1328	benign	0.213	Stabilizing	0.22	N	0.389	neutral	None	None	None	None	N
Q/W	0.347	ambiguous	0.3554	ambiguous	-0.41	Destabilizing	0.958	D	0.363	neutral	None	None	None	None	N
Q/Y	0.2488	likely_benign	0.2395	benign	-0.1	Destabilizing	0.859	D	0.391	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.