TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17572	52939;52940;52941	chr2:178608073;178608072;178608071	chr2:179472800;179472799;179472798
N2AB	15931	48016;48017;48018	chr2:178608073;178608072;178608071	chr2:179472800;179472799;179472798
N2A	15004	45235;45236;45237	chr2:178608073;178608072;178608071	chr2:179472800;179472799;179472798
N2B	8507	25744;25745;25746	chr2:178608073;178608072;178608071	chr2:179472800;179472799;179472798
Novex-1	8632	26119;26120;26121	chr2:178608073;178608072;178608071	chr2:179472800;179472799;179472798
Novex-2	8699	26320;26321;26322	chr2:178608073;178608072;178608071	chr2:179472800;179472799;179472798
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: Fn3-16
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1501
• Predicted PPI site: N

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/E	rs867992198	None	1.0	N	0.753	0.397	0.37262878642	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
G/E	rs867992198	None	1.0	N	0.753	0.397	0.37262878642	gnomAD-4.0.0	6.57929E-06	None	None	None	None	N	None	2.40964E-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	0.3653	ambiguous	0.3474	ambiguous	-0.868	Destabilizing	0.998	D	0.666	neutral	N	0.466127048	None	None	N
G/C	0.6488	likely_pathogenic	0.6707	pathogenic	-1.147	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
G/D	0.8069	likely_pathogenic	0.8298	pathogenic	-1.972	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/E	0.7864	likely_pathogenic	0.8187	pathogenic	-1.978	Destabilizing	1.0	D	0.753	deleterious	N	0.45944155	None	None	N
G/F	0.895	likely_pathogenic	0.9045	pathogenic	-1.047	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/H	0.9177	likely_pathogenic	0.9231	pathogenic	-1.562	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/I	0.861	likely_pathogenic	0.8742	pathogenic	-0.36	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/K	0.9302	likely_pathogenic	0.9434	pathogenic	-1.381	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
G/L	0.8257	likely_pathogenic	0.838	pathogenic	-0.36	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/M	0.8828	likely_pathogenic	0.8946	pathogenic	-0.424	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/N	0.8172	likely_pathogenic	0.8521	pathogenic	-1.218	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/P	0.9844	likely_pathogenic	0.989	pathogenic	-0.49	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/Q	0.8484	likely_pathogenic	0.8713	pathogenic	-1.366	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/R	0.882	likely_pathogenic	0.8925	pathogenic	-1.137	Destabilizing	0.909	D	0.625	neutral	N	0.487967513	None	None	N
G/S	0.2375	likely_benign	0.2267	benign	-1.425	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
G/T	0.6566	likely_pathogenic	0.6894	pathogenic	-1.364	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
G/V	0.7957	likely_pathogenic	0.809	pathogenic	-0.49	Destabilizing	1.0	D	0.788	deleterious	N	0.499741892	None	None	N
G/W	0.91	likely_pathogenic	0.9052	pathogenic	-1.506	Destabilizing	1.0	D	0.742	deleterious	N	0.50050236	None	None	N
G/Y	0.8702	likely_pathogenic	0.8808	pathogenic	-1.071	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N

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.