TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15737	47434;47435;47436	chr2:178618249;178618248;178618247	chr2:179482976;179482975;179482974
N2AB	14096	42511;42512;42513	chr2:178618249;178618248;178618247	chr2:179482976;179482975;179482974
N2A	13169	39730;39731;39732	chr2:178618249;178618248;178618247	chr2:179482976;179482975;179482974
N2B	6672	20239;20240;20241	chr2:178618249;178618248;178618247	chr2:179482976;179482975;179482974
Novex-1	6797	20614;20615;20616	chr2:178618249;178618248;178618247	chr2:179482976;179482975;179482974
Novex-2	6864	20815;20816;20817	chr2:178618249;178618248;178618247	chr2:179482976;179482975;179482974
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-1
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.7164
• 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
R/G	rs376440087	None	1.0	N	0.567	0.314	None	gnomAD-4.0.0	1.59313E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8622E-06	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
R/A	0.7701	likely_pathogenic	0.7518	pathogenic	0.006	Stabilizing	0.999	D	0.583	neutral	None	None	None	None	I
R/C	0.7002	likely_pathogenic	0.617	pathogenic	-0.214	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
R/D	0.8933	likely_pathogenic	0.8806	pathogenic	-0.116	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	I
R/E	0.704	likely_pathogenic	0.678	pathogenic	-0.062	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	I
R/F	0.9174	likely_pathogenic	0.8928	pathogenic	-0.289	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
R/G	0.7407	likely_pathogenic	0.7379	pathogenic	-0.164	Destabilizing	1.0	D	0.567	neutral	N	0.460445931	None	None	I
R/H	0.3697	ambiguous	0.3312	benign	-0.66	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
R/I	0.6601	likely_pathogenic	0.6007	pathogenic	0.412	Stabilizing	1.0	D	0.661	neutral	N	0.480305529	None	None	I
R/K	0.3244	likely_benign	0.278	benign	-0.095	Destabilizing	0.997	D	0.407	neutral	N	0.464189806	None	None	I
R/L	0.6278	likely_pathogenic	0.6041	pathogenic	0.412	Stabilizing	1.0	D	0.567	neutral	None	None	None	None	I
R/M	0.7427	likely_pathogenic	0.6942	pathogenic	-0.003	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	I
R/N	0.8639	likely_pathogenic	0.8344	pathogenic	0.06	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
R/P	0.8992	likely_pathogenic	0.8593	pathogenic	0.296	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	I
R/Q	0.2958	likely_benign	0.2773	benign	-0.018	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
R/S	0.8457	likely_pathogenic	0.8401	pathogenic	-0.244	Destabilizing	1.0	D	0.623	neutral	N	0.452975839	None	None	I
R/T	0.6886	likely_pathogenic	0.6426	pathogenic	-0.065	Destabilizing	1.0	D	0.616	neutral	N	0.476474893	None	None	I
R/V	0.7337	likely_pathogenic	0.6983	pathogenic	0.296	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	I
R/W	0.6201	likely_pathogenic	0.579	pathogenic	-0.398	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
R/Y	0.8201	likely_pathogenic	0.7869	pathogenic	0.024	Stabilizing	1.0	D	0.675	prob.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.