TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5716	17371;17372;17373	chr2:178731729;178731728;178731727	chr2:179596456;179596455;179596454
N2AB	5399	16420;16421;16422	chr2:178731729;178731728;178731727	chr2:179596456;179596455;179596454
N2A	4472	13639;13640;13641	chr2:178731729;178731728;178731727	chr2:179596456;179596455;179596454
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-40
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2204
• 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
G/A	None	None	1.0	D	0.74	0.686	0.605229780939	gnomAD-4.0.0	6.84536E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65733E-05
G/D	rs952474808	None	1.0	D	0.846	0.68	0.664105290246	gnomAD-4.0.0	6.16082E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19923E-06	0	1.65733E-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
G/A	0.7621	likely_pathogenic	0.5996	pathogenic	-0.248	Destabilizing	1.0	D	0.74	deleterious	D	0.586906453	None	None	I
G/C	0.9397	likely_pathogenic	0.8775	pathogenic	-0.867	Destabilizing	1.0	D	0.795	deleterious	D	0.613655391	None	None	I
G/D	0.908	likely_pathogenic	0.7806	pathogenic	-0.519	Destabilizing	1.0	D	0.846	deleterious	D	0.576984094	None	None	I
G/E	0.9519	likely_pathogenic	0.8717	pathogenic	-0.692	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/F	0.989	likely_pathogenic	0.9802	pathogenic	-1.06	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/H	0.9864	likely_pathogenic	0.9687	pathogenic	-0.442	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
G/I	0.9857	likely_pathogenic	0.9696	pathogenic	-0.483	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/K	0.9867	likely_pathogenic	0.9721	pathogenic	-0.637	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/L	0.9842	likely_pathogenic	0.9674	pathogenic	-0.483	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/M	0.9906	likely_pathogenic	0.9795	pathogenic	-0.473	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
G/N	0.9529	likely_pathogenic	0.9013	pathogenic	-0.334	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/P	0.998	likely_pathogenic	0.997	pathogenic	-0.375	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/Q	0.9695	likely_pathogenic	0.9282	pathogenic	-0.639	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/R	0.9626	likely_pathogenic	0.9222	pathogenic	-0.205	Destabilizing	1.0	D	0.851	deleterious	D	0.612646369	None	None	I
G/S	0.6344	likely_pathogenic	0.4904	ambiguous	-0.461	Destabilizing	1.0	D	0.793	deleterious	D	0.574460643	None	None	I
G/T	0.9213	likely_pathogenic	0.8593	pathogenic	-0.57	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/V	0.9683	likely_pathogenic	0.9366	pathogenic	-0.375	Destabilizing	1.0	D	0.817	deleterious	D	0.629271143	None	None	I
G/W	0.9829	likely_pathogenic	0.9654	pathogenic	-1.176	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/Y	0.9831	likely_pathogenic	0.9639	pathogenic	-0.835	Destabilizing	1.0	D	0.824	deleterious	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.