TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14138	42637;42638;42639	chr2:178634369;178634368;178634367	chr2:179499096;179499095;179499094
N2AB	12497	37714;37715;37716	chr2:178634369;178634368;178634367	chr2:179499096;179499095;179499094
N2A	11570	34933;34934;34935	chr2:178634369;178634368;178634367	chr2:179499096;179499095;179499094
N2B	5073	15442;15443;15444	chr2:178634369;178634368;178634367	chr2:179499096;179499095;179499094
Novex-1	5198	15817;15818;15819	chr2:178634369;178634368;178634367	chr2:179499096;179499095;179499094
Novex-2	5265	16018;16019;16020	chr2:178634369;178634368;178634367	chr2:179499096;179499095;179499094
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-91
• Domain position: 85
• Structural Position: 178
• Q(SASA): 0.4684
• 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	None	None	0.044	N	0.256	0.099	0.104622674875	gnomAD-4.0.0	6.89099E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.01369E-07	0	0
T/P	rs376500376	-0.063	0.31	N	0.394	0.234	None	gnomAD-2.1.1	1.48E-05	None	None	None	None	I	None	1.67462E-04	0	None	0	0	None	0	None	0	0	0
T/P	rs376500376	-0.063	0.31	N	0.394	0.234	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	I	None	1.44788E-04	0	0	0	0	None	0	0	0	0	0
T/P	rs376500376	-0.063	0.31	N	0.394	0.234	None	gnomAD-4.0.0	5.61355E-06	None	None	None	None	I	None	1.21737E-04	0	None	0	0	None	0	0	0	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
T/A	0.108	likely_benign	0.1195	benign	-0.457	Destabilizing	0.044	N	0.256	neutral	N	0.447011688	None	None	I
T/C	0.6838	likely_pathogenic	0.6844	pathogenic	-0.374	Destabilizing	0.96	D	0.306	neutral	None	None	None	None	I
T/D	0.3477	ambiguous	0.4288	ambiguous	0.423	Stabilizing	0.057	N	0.289	neutral	None	None	None	None	I
T/E	0.1285	likely_benign	0.1836	benign	0.395	Stabilizing	None	N	0.126	neutral	None	None	None	None	I
T/F	0.5437	ambiguous	0.5739	pathogenic	-0.744	Destabilizing	0.864	D	0.339	neutral	None	None	None	None	I
T/G	0.3135	likely_benign	0.3862	ambiguous	-0.652	Destabilizing	0.227	N	0.318	neutral	None	None	None	None	I
T/H	0.3507	ambiguous	0.3684	ambiguous	-0.848	Destabilizing	0.676	D	0.319	neutral	None	None	None	None	I
T/I	0.3428	ambiguous	0.3648	ambiguous	-0.051	Destabilizing	0.612	D	0.375	neutral	N	0.441182261	None	None	I
T/K	0.1691	likely_benign	0.1992	benign	-0.355	Destabilizing	0.044	N	0.316	neutral	N	0.395847323	None	None	I
T/L	0.1867	likely_benign	0.2072	benign	-0.051	Destabilizing	0.227	N	0.311	neutral	None	None	None	None	I
T/M	0.1505	likely_benign	0.145	benign	-0.058	Destabilizing	0.864	D	0.285	neutral	None	None	None	None	I
T/N	0.1524	likely_benign	0.1699	benign	-0.264	Destabilizing	0.227	N	0.239	neutral	None	None	None	None	I
T/P	0.4134	ambiguous	0.4008	ambiguous	-0.155	Destabilizing	0.31	N	0.394	neutral	N	0.454289891	None	None	I
T/Q	0.1774	likely_benign	0.2155	benign	-0.386	Destabilizing	0.128	N	0.328	neutral	None	None	None	None	I
T/R	0.2007	likely_benign	0.2141	benign	-0.149	Destabilizing	0.181	N	0.346	neutral	N	0.417707486	None	None	I
T/S	0.1357	likely_benign	0.1515	benign	-0.542	Destabilizing	0.044	N	0.301	neutral	N	0.448995558	None	None	I
T/V	0.2338	likely_benign	0.2496	benign	-0.155	Destabilizing	0.227	N	0.235	neutral	None	None	None	None	I
T/W	0.7862	likely_pathogenic	0.7909	pathogenic	-0.74	Destabilizing	0.96	D	0.343	neutral	None	None	None	None	I
T/Y	0.4846	ambiguous	0.5067	ambiguous	-0.457	Destabilizing	0.864	D	0.344	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.