TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15162	45709;45710;45711	chr2:178621234;178621233;178621232	chr2:179485961;179485960;179485959
N2AB	13521	40786;40787;40788	chr2:178621234;178621233;178621232	chr2:179485961;179485960;179485959
N2A	12594	38005;38006;38007	chr2:178621234;178621233;178621232	chr2:179485961;179485960;179485959
N2B	6097	18514;18515;18516	chr2:178621234;178621233;178621232	chr2:179485961;179485960;179485959
Novex-1	6222	18889;18890;18891	chr2:178621234;178621233;178621232	chr2:179485961;179485960;179485959
Novex-2	6289	19090;19091;19092	chr2:178621234;178621233;178621232	chr2:179485961;179485960;179485959
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-103
• Domain position: 43
• Structural Position: 73
• Q(SASA): 0.3068
• 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	None	None	0.999	N	0.7	0.304	0.322510055762	gnomAD-4.0.0	1.59429E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88466E-05	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	0.2005	likely_benign	0.1842	benign	-0.241	Destabilizing	0.999	D	0.54	neutral	D	0.52643287	None	None	N
G/C	0.3773	ambiguous	0.2993	benign	-0.851	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
G/D	0.2102	likely_benign	0.1859	benign	-0.47	Destabilizing	0.852	D	0.518	neutral	None	None	None	None	N
G/E	0.3486	ambiguous	0.3013	benign	-0.632	Destabilizing	0.999	D	0.7	prob.neutral	N	0.467257779	None	None	N
G/F	0.8237	likely_pathogenic	0.7555	pathogenic	-0.98	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
G/H	0.6081	likely_pathogenic	0.4992	ambiguous	-0.463	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
G/I	0.5951	likely_pathogenic	0.5344	ambiguous	-0.396	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
G/K	0.5682	likely_pathogenic	0.4624	ambiguous	-0.717	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
G/L	0.6565	likely_pathogenic	0.575	pathogenic	-0.396	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
G/M	0.7138	likely_pathogenic	0.6441	pathogenic	-0.454	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
G/N	0.2934	likely_benign	0.2557	benign	-0.373	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
G/P	0.9533	likely_pathogenic	0.9324	pathogenic	-0.312	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
G/Q	0.5072	ambiguous	0.4171	ambiguous	-0.651	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
G/R	0.4534	ambiguous	0.3643	ambiguous	-0.284	Destabilizing	1.0	D	0.74	deleterious	D	0.540278595	None	None	N
G/S	0.0996	likely_benign	0.094	benign	-0.527	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
G/T	0.1854	likely_benign	0.1737	benign	-0.616	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
G/V	0.4043	ambiguous	0.3593	ambiguous	-0.312	Destabilizing	1.0	D	0.757	deleterious	D	0.582718623	None	None	N
G/W	0.7093	likely_pathogenic	0.6132	pathogenic	-1.127	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
G/Y	0.7464	likely_pathogenic	0.6776	pathogenic	-0.775	Destabilizing	1.0	D	0.741	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.