TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8439	25540;25541;25542	chr2:178717559;178717558;178717557	chr2:179582286;179582285;179582284
N2AB	8122	24589;24590;24591	chr2:178717559;178717558;178717557	chr2:179582286;179582285;179582284
N2A	7195	21808;21809;21810	chr2:178717559;178717558;178717557	chr2:179582286;179582285;179582284
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: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-69
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2301
• 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/R	rs1177073291	None	1.0	N	0.857	0.635	0.689113965555	gnomAD-4.0.0	6.84901E-07	None	None	None	None	I	None	2.99347E-05	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
G/A	0.8218	likely_pathogenic	0.7625	pathogenic	-0.421	Destabilizing	1.0	D	0.751	deleterious	N	0.504389927	None	None	I
G/C	0.9644	likely_pathogenic	0.9429	pathogenic	-0.902	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/D	0.9507	likely_pathogenic	0.9107	pathogenic	-0.707	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/E	0.9646	likely_pathogenic	0.9299	pathogenic	-0.875	Destabilizing	1.0	D	0.829	deleterious	N	0.513606639	None	None	I
G/F	0.9909	likely_pathogenic	0.9843	pathogenic	-1.153	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/H	0.9877	likely_pathogenic	0.9737	pathogenic	-0.675	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/I	0.9891	likely_pathogenic	0.9795	pathogenic	-0.557	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/K	0.9899	likely_pathogenic	0.9775	pathogenic	-0.914	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/L	0.9842	likely_pathogenic	0.9723	pathogenic	-0.557	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/M	0.9922	likely_pathogenic	0.9852	pathogenic	-0.505	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
G/N	0.9754	likely_pathogenic	0.9548	pathogenic	-0.548	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
G/P	0.9984	likely_pathogenic	0.9975	pathogenic	-0.479	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
G/Q	0.9761	likely_pathogenic	0.9517	pathogenic	-0.861	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/R	0.9719	likely_pathogenic	0.9429	pathogenic	-0.431	Destabilizing	1.0	D	0.857	deleterious	N	0.514367108	None	None	I
G/S	0.8034	likely_pathogenic	0.7288	pathogenic	-0.683	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/T	0.9623	likely_pathogenic	0.937	pathogenic	-0.786	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/V	0.9725	likely_pathogenic	0.9521	pathogenic	-0.479	Destabilizing	1.0	D	0.831	deleterious	D	0.537751282	None	None	I
G/W	0.9868	likely_pathogenic	0.9771	pathogenic	-1.292	Destabilizing	1.0	D	0.812	deleterious	D	0.526483881	None	None	I
G/Y	0.9861	likely_pathogenic	0.9735	pathogenic	-0.957	Destabilizing	1.0	D	0.834	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.