TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23978	72157;72158;72159	chr2:178574200;178574199;178574198	chr2:179438927;179438926;179438925
N2AB	22337	67234;67235;67236	chr2:178574200;178574199;178574198	chr2:179438927;179438926;179438925
N2A	21410	64453;64454;64455	chr2:178574200;178574199;178574198	chr2:179438927;179438926;179438925
N2B	14913	44962;44963;44964	chr2:178574200;178574199;178574198	chr2:179438927;179438926;179438925
Novex-1	15038	45337;45338;45339	chr2:178574200;178574199;178574198	chr2:179438927;179438926;179438925
Novex-2	15105	45538;45539;45540	chr2:178574200;178574199;178574198	chr2:179438927;179438926;179438925
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-62
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.6934
• 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
N/H	rs1346537219	-0.64	1.0	N	0.708	0.495	0.252162846088	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
N/H	rs1346537219	-0.64	1.0	N	0.708	0.495	0.252162846088	gnomAD-4.0.0	1.59203E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85956E-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
N/A	0.3002	likely_benign	0.3213	benign	-0.392	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
N/C	0.4671	ambiguous	0.4775	ambiguous	0.297	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
N/D	0.321	likely_benign	0.3027	benign	0.245	Stabilizing	0.999	D	0.613	neutral	N	0.511496901	None	None	I
N/E	0.7324	likely_pathogenic	0.7235	pathogenic	0.194	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
N/F	0.7673	likely_pathogenic	0.7911	pathogenic	-0.875	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
N/G	0.3517	ambiguous	0.3608	ambiguous	-0.523	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	I
N/H	0.1873	likely_benign	0.1925	benign	-0.597	Destabilizing	1.0	D	0.708	prob.delet.	N	0.471079296	None	None	I
N/I	0.346	ambiguous	0.37	ambiguous	-0.138	Destabilizing	1.0	D	0.872	deleterious	N	0.512190335	None	None	I
N/K	0.6584	likely_pathogenic	0.662	pathogenic	0.259	Stabilizing	1.0	D	0.697	prob.neutral	N	0.498258245	None	None	I
N/L	0.3653	ambiguous	0.3909	ambiguous	-0.138	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
N/M	0.5046	ambiguous	0.5379	ambiguous	0.264	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
N/P	0.5095	ambiguous	0.4912	ambiguous	-0.198	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
N/Q	0.5709	likely_pathogenic	0.5801	pathogenic	-0.251	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
N/R	0.6918	likely_pathogenic	0.7035	pathogenic	0.311	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
N/S	0.0906	likely_benign	0.0945	benign	-0.019	Destabilizing	0.999	D	0.603	neutral	N	0.515035852	None	None	I
N/T	0.1785	likely_benign	0.1809	benign	0.071	Stabilizing	0.999	D	0.673	neutral	N	0.494335293	None	None	I
N/V	0.2961	likely_benign	0.3191	benign	-0.198	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
N/W	0.932	likely_pathogenic	0.9354	pathogenic	-0.853	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
N/Y	0.3518	ambiguous	0.3606	ambiguous	-0.574	Destabilizing	1.0	D	0.843	deleterious	N	0.498235679	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.