TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17090	51493;51494;51495	chr2:178610258;178610257;178610256	chr2:179474985;179474984;179474983
N2AB	15449	46570;46571;46572	chr2:178610258;178610257;178610256	chr2:179474985;179474984;179474983
N2A	14522	43789;43790;43791	chr2:178610258;178610257;178610256	chr2:179474985;179474984;179474983
N2B	8025	24298;24299;24300	chr2:178610258;178610257;178610256	chr2:179474985;179474984;179474983
Novex-1	8150	24673;24674;24675	chr2:178610258;178610257;178610256	chr2:179474985;179474984;179474983
Novex-2	8217	24874;24875;24876	chr2:178610258;178610257;178610256	chr2:179474985;179474984;179474983
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: Fn3-12
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.4123
• 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	1.0	N	0.682	0.488	0.511220899679	gnomAD-4.0.0	1.59281E-06	None	None	None	None	N	None	0	2.28697E-05	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	0.3571	ambiguous	0.3587	ambiguous	-0.259	Destabilizing	1.0	D	0.535	neutral	N	0.520119171	None	None	N
G/C	0.7092	likely_pathogenic	0.6837	pathogenic	-0.905	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
G/D	0.8545	likely_pathogenic	0.7829	pathogenic	-0.784	Destabilizing	1.0	D	0.594	neutral	None	None	None	None	N
G/E	0.8247	likely_pathogenic	0.7738	pathogenic	-0.942	Destabilizing	1.0	D	0.682	prob.neutral	N	0.517385511	None	None	N
G/F	0.9304	likely_pathogenic	0.916	pathogenic	-0.99	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
G/H	0.8988	likely_pathogenic	0.8623	pathogenic	-0.405	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
G/I	0.8147	likely_pathogenic	0.7977	pathogenic	-0.443	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
G/K	0.9416	likely_pathogenic	0.9196	pathogenic	-0.883	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
G/L	0.8353	likely_pathogenic	0.812	pathogenic	-0.443	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
G/M	0.8405	likely_pathogenic	0.835	pathogenic	-0.616	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
G/N	0.651	likely_pathogenic	0.6204	pathogenic	-0.504	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
G/P	0.97	likely_pathogenic	0.9686	pathogenic	-0.352	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
G/Q	0.7975	likely_pathogenic	0.7633	pathogenic	-0.794	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
G/R	0.9004	likely_pathogenic	0.859	pathogenic	-0.398	Destabilizing	1.0	D	0.695	prob.neutral	N	0.485842643	None	None	N
G/S	0.2366	likely_benign	0.225	benign	-0.611	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
G/T	0.4613	ambiguous	0.4565	ambiguous	-0.709	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
G/V	0.6857	likely_pathogenic	0.6594	pathogenic	-0.352	Destabilizing	1.0	D	0.717	prob.delet.	N	0.481678814	None	None	N
G/W	0.9092	likely_pathogenic	0.8714	pathogenic	-1.129	Destabilizing	1.0	D	0.711	prob.delet.	N	0.496428934	None	None	N
G/Y	0.9258	likely_pathogenic	0.8963	pathogenic	-0.802	Destabilizing	1.0	D	0.701	prob.neutral	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.