TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4796	14611;14612;14613	chr2:178736060;178736059;178736058	chr2:179600787;179600786;179600785
N2AB	4479	13660;13661;13662	chr2:178736060;178736059;178736058	chr2:179600787;179600786;179600785
N2A	3552	10879;10880;10881	chr2:178736060;178736059;178736058	chr2:179600787;179600786;179600785
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-31
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4409
• 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
T/A	rs780971372	-0.663	None	N	0.121	0.07	0.130388298395	gnomAD-2.1.1	1.8E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.86E-05	0
T/A	rs780971372	-0.663	None	N	0.121	0.07	0.130388298395	gnomAD-4.0.0	1.67824E-05	None	None	None	None	I	None	3.10347E-05	0	None	0	0	None	0	3.57015E-04	1.45896E-05	0	8.48522E-05

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
T/A	0.0617	likely_benign	0.0656	benign	-0.815	Destabilizing	None	N	0.121	neutral	N	0.487274376	None	None	I
T/C	0.3107	likely_benign	0.3551	ambiguous	-0.429	Destabilizing	0.356	N	0.304	neutral	None	None	None	None	I
T/D	0.3379	likely_benign	0.3794	ambiguous	0.465	Stabilizing	0.038	N	0.279	neutral	None	None	None	None	I
T/E	0.2609	likely_benign	0.3027	benign	0.472	Stabilizing	0.001	N	0.193	neutral	None	None	None	None	I
T/F	0.161	likely_benign	0.1919	benign	-0.956	Destabilizing	0.214	N	0.37	neutral	None	None	None	None	I
T/G	0.1861	likely_benign	0.209	benign	-1.058	Destabilizing	0.016	N	0.245	neutral	None	None	None	None	I
T/H	0.2043	likely_benign	0.2199	benign	-1.213	Destabilizing	0.628	D	0.29	neutral	None	None	None	None	I
T/I	0.0962	likely_benign	0.1101	benign	-0.262	Destabilizing	None	N	0.19	neutral	N	0.39908953	None	None	I
T/K	0.1744	likely_benign	0.1994	benign	-0.35	Destabilizing	0.072	N	0.267	neutral	None	None	None	None	I
T/L	0.0735	likely_benign	0.0814	benign	-0.262	Destabilizing	0.002	N	0.215	neutral	None	None	None	None	I
T/M	0.0792	likely_benign	0.088	benign	-0.123	Destabilizing	0.002	N	0.199	neutral	None	None	None	None	I
T/N	0.1036	likely_benign	0.1115	benign	-0.31	Destabilizing	0.055	N	0.247	neutral	N	0.495912429	None	None	I
T/P	0.4218	ambiguous	0.4714	ambiguous	-0.415	Destabilizing	0.106	N	0.355	neutral	N	0.512631981	None	None	I
T/Q	0.1834	likely_benign	0.1995	benign	-0.415	Destabilizing	0.072	N	0.38	neutral	None	None	None	None	I
T/R	0.1288	likely_benign	0.1498	benign	-0.195	Destabilizing	0.072	N	0.379	neutral	None	None	None	None	I
T/S	0.0805	likely_benign	0.0847	benign	-0.692	Destabilizing	None	N	0.122	neutral	N	0.462911917	None	None	I
T/V	0.0831	likely_benign	0.0877	benign	-0.415	Destabilizing	None	N	0.104	neutral	None	None	None	None	I
T/W	0.5238	ambiguous	0.6096	pathogenic	-0.867	Destabilizing	0.864	D	0.334	neutral	None	None	None	None	I
T/Y	0.207	likely_benign	0.239	benign	-0.613	Destabilizing	0.356	N	0.338	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.