TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22356	67291;67292;67293	chr2:178580221;178580220;178580219	chr2:179444948;179444947;179444946
N2AB	20715	62368;62369;62370	chr2:178580221;178580220;178580219	chr2:179444948;179444947;179444946
N2A	19788	59587;59588;59589	chr2:178580221;178580220;178580219	chr2:179444948;179444947;179444946
N2B	13291	40096;40097;40098	chr2:178580221;178580220;178580219	chr2:179444948;179444947;179444946
Novex-1	13416	40471;40472;40473	chr2:178580221;178580220;178580219	chr2:179444948;179444947;179444946
Novex-2	13483	40672;40673;40674	chr2:178580221;178580220;178580219	chr2:179444948;179444947;179444946
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: Fn3-50
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1834
• 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/R	rs763997790	-0.969	0.997	N	0.815	0.501	0.541648499649	gnomAD-4.0.0	1.59442E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86133E-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
G/A	0.4766	ambiguous	0.4932	ambiguous	-0.867	Destabilizing	0.983	D	0.669	neutral	N	0.489446586	None	None	N
G/C	0.8387	likely_pathogenic	0.8559	pathogenic	-1.354	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/D	0.9242	likely_pathogenic	0.9612	pathogenic	-2.4	Highly Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
G/E	0.9335	likely_pathogenic	0.9574	pathogenic	-2.402	Highly Destabilizing	0.997	D	0.795	deleterious	D	0.526945316	None	None	N
G/F	0.9733	likely_pathogenic	0.9771	pathogenic	-1.094	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/H	0.9818	likely_pathogenic	0.9869	pathogenic	-1.389	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/I	0.9663	likely_pathogenic	0.9675	pathogenic	-0.388	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
G/K	0.989	likely_pathogenic	0.9916	pathogenic	-1.322	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
G/L	0.9344	likely_pathogenic	0.9422	pathogenic	-0.388	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
G/M	0.9637	likely_pathogenic	0.9664	pathogenic	-0.513	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/N	0.9358	likely_pathogenic	0.9548	pathogenic	-1.3	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
G/P	0.9968	likely_pathogenic	0.9972	pathogenic	-0.51	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
G/Q	0.9576	likely_pathogenic	0.9661	pathogenic	-1.484	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
G/R	0.9722	likely_pathogenic	0.9777	pathogenic	-1.04	Destabilizing	0.997	D	0.815	deleterious	N	0.516945364	None	None	N
G/S	0.3556	ambiguous	0.3963	ambiguous	-1.465	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	N
G/T	0.8611	likely_pathogenic	0.8821	pathogenic	-1.405	Destabilizing	0.713	D	0.579	neutral	None	None	None	None	N
G/V	0.9383	likely_pathogenic	0.9436	pathogenic	-0.51	Destabilizing	0.995	D	0.788	deleterious	D	0.522732262	None	None	N
G/W	0.9725	likely_pathogenic	0.9782	pathogenic	-1.529	Destabilizing	1.0	D	0.773	deleterious	D	0.541090006	None	None	N
G/Y	0.9706	likely_pathogenic	0.9766	pathogenic	-1.093	Destabilizing	1.0	D	0.823	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.