TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17333	52222;52223;52224	chr2:178609313;178609312;178609311	chr2:179474040;179474039;179474038
N2AB	15692	47299;47300;47301	chr2:178609313;178609312;178609311	chr2:179474040;179474039;179474038
N2A	14765	44518;44519;44520	chr2:178609313;178609312;178609311	chr2:179474040;179474039;179474038
N2B	8268	25027;25028;25029	chr2:178609313;178609312;178609311	chr2:179474040;179474039;179474038
Novex-1	8393	25402;25403;25404	chr2:178609313;178609312;178609311	chr2:179474040;179474039;179474038
Novex-2	8460	25603;25604;25605	chr2:178609313;178609312;178609311	chr2:179474040;179474039;179474038
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-112
• Domain position: 83
• Structural Position: 137
• Q(SASA): 0.306
• 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/H	None	None	0.196	N	0.469	0.083	0.247872288689	gnomAD-4.0.0	1.60681E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88317E-06	0	0
Q/P	None	None	0.065	N	0.572	0.267	0.301122078929	gnomAD-4.0.0	5.49847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.31697E-06	1.1714E-05	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	0.19	likely_benign	0.1733	benign	0.175	Stabilizing	0.002	N	0.354	neutral	None	None	None	None	N
Q/C	0.3652	ambiguous	0.4077	ambiguous	0.179	Stabilizing	0.497	N	0.623	neutral	None	None	None	None	N
Q/D	0.5104	ambiguous	0.4777	ambiguous	-1.748	Destabilizing	0.009	N	0.416	neutral	None	None	None	None	N
Q/E	0.1041	likely_benign	0.0916	benign	-1.649	Destabilizing	None	N	0.161	neutral	N	0.486727035	None	None	N
Q/F	0.4175	ambiguous	0.4109	ambiguous	0.09	Stabilizing	None	N	0.524	neutral	None	None	None	None	N
Q/G	0.3094	likely_benign	0.2907	benign	-0.159	Destabilizing	0.018	N	0.449	neutral	None	None	None	None	N
Q/H	0.1433	likely_benign	0.1554	benign	-0.519	Destabilizing	0.196	N	0.469	neutral	N	0.489504672	None	None	N
Q/I	0.2064	likely_benign	0.2044	benign	1.003	Stabilizing	None	N	0.496	neutral	None	None	None	None	N
Q/K	0.0868	likely_benign	0.0994	benign	-0.096	Destabilizing	0.003	N	0.415	neutral	N	0.466525121	None	None	N
Q/L	0.1198	likely_benign	0.1198	benign	1.003	Stabilizing	0.001	N	0.459	neutral	N	0.470797577	None	None	N
Q/M	0.2632	likely_benign	0.26	benign	1.423	Stabilizing	0.138	N	0.507	neutral	None	None	None	None	N
Q/N	0.3014	likely_benign	0.2904	benign	-0.845	Destabilizing	0.018	N	0.519	neutral	None	None	None	None	N
Q/P	0.7914	likely_pathogenic	0.7874	pathogenic	0.76	Stabilizing	0.065	N	0.572	neutral	N	0.489758161	None	None	N
Q/R	0.0858	likely_benign	0.0982	benign	-0.132	Destabilizing	0.007	N	0.565	neutral	N	0.493807723	None	None	N
Q/S	0.1944	likely_benign	0.1742	benign	-0.686	Destabilizing	None	N	0.159	neutral	None	None	None	None	N
Q/T	0.1442	likely_benign	0.1438	benign	-0.425	Destabilizing	0.004	N	0.369	neutral	None	None	None	None	N
Q/V	0.1466	likely_benign	0.145	benign	0.76	Stabilizing	None	N	0.365	neutral	None	None	None	None	N
Q/W	0.4182	ambiguous	0.4706	ambiguous	-0.115	Destabilizing	0.788	D	0.623	neutral	None	None	None	None	N
Q/Y	0.2883	likely_benign	0.2939	benign	0.359	Stabilizing	0.022	N	0.573	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.