TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15977	48154;48155;48156	chr2:178616960;178616959;178616958	chr2:179481687;179481686;179481685
N2AB	14336	43231;43232;43233	chr2:178616960;178616959;178616958	chr2:179481687;179481686;179481685
N2A	13409	40450;40451;40452	chr2:178616960;178616959;178616958	chr2:179481687;179481686;179481685
N2B	6912	20959;20960;20961	chr2:178616960;178616959;178616958	chr2:179481687;179481686;179481685
Novex-1	7037	21334;21335;21336	chr2:178616960;178616959;178616958	chr2:179481687;179481686;179481685
Novex-2	7104	21535;21536;21537	chr2:178616960;178616959;178616958	chr2:179481687;179481686;179481685
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-109
• Domain position: 10
• Structural Position: 24
• Q(SASA): 0.3936
• 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
P/S	None	None	1.0	N	0.729	0.368	0.258779203287	gnomAD-4.0.0	1.59343E-06	None	None	None	None	I	None	0	0	None	0	2.7784E-05	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
P/A	0.5663	likely_pathogenic	0.5517	ambiguous	-0.683	Destabilizing	1.0	D	0.677	prob.neutral	N	0.444868925	None	None	I
P/C	0.945	likely_pathogenic	0.9447	pathogenic	-0.661	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
P/D	0.8219	likely_pathogenic	0.8247	pathogenic	-0.523	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
P/E	0.7788	likely_pathogenic	0.7586	pathogenic	-0.637	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
P/F	0.9864	likely_pathogenic	0.9841	pathogenic	-0.844	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
P/G	0.5538	ambiguous	0.5582	ambiguous	-0.831	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/H	0.8416	likely_pathogenic	0.8295	pathogenic	-0.342	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/I	0.9726	likely_pathogenic	0.9708	pathogenic	-0.44	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/K	0.8747	likely_pathogenic	0.8647	pathogenic	-0.612	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
P/L	0.8402	likely_pathogenic	0.8254	pathogenic	-0.44	Destabilizing	1.0	D	0.747	deleterious	N	0.499504563	None	None	I
P/M	0.9521	likely_pathogenic	0.9467	pathogenic	-0.37	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
P/N	0.8215	likely_pathogenic	0.8206	pathogenic	-0.34	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/Q	0.7686	likely_pathogenic	0.7473	pathogenic	-0.62	Destabilizing	1.0	D	0.731	prob.delet.	N	0.497625357	None	None	I
P/R	0.7768	likely_pathogenic	0.7589	pathogenic	-0.01	Destabilizing	1.0	D	0.742	deleterious	N	0.433927109	None	None	I
P/S	0.6402	likely_pathogenic	0.6283	pathogenic	-0.706	Destabilizing	1.0	D	0.729	prob.delet.	N	0.456430052	None	None	I
P/T	0.6691	likely_pathogenic	0.6411	pathogenic	-0.724	Destabilizing	1.0	D	0.715	prob.delet.	N	0.433927109	None	None	I
P/V	0.9301	likely_pathogenic	0.9261	pathogenic	-0.486	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
P/W	0.9866	likely_pathogenic	0.9843	pathogenic	-0.903	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
P/Y	0.9637	likely_pathogenic	0.9631	pathogenic	-0.627	Destabilizing	1.0	D	0.733	prob.delet.	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.