TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26722	80389;80390;80391	chr2:178565968;178565967;178565966	chr2:179430695;179430694;179430693
N2AB	25081	75466;75467;75468	chr2:178565968;178565967;178565966	chr2:179430695;179430694;179430693
N2A	24154	72685;72686;72687	chr2:178565968;178565967;178565966	chr2:179430695;179430694;179430693
N2B	17657	53194;53195;53196	chr2:178565968;178565967;178565966	chr2:179430695;179430694;179430693
Novex-1	17782	53569;53570;53571	chr2:178565968;178565967;178565966	chr2:179430695;179430694;179430693
Novex-2	17849	53770;53771;53772	chr2:178565968;178565967;178565966	chr2:179430695;179430694;179430693
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-82
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.3008
• 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
K/Q	None	None	0.987	N	0.819	0.451	0.322230723748	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
K/A	0.9679	likely_pathogenic	0.9727	pathogenic	-1.426	Destabilizing	0.996	D	0.712	prob.delet.	None	None	None	None	N
K/C	0.8931	likely_pathogenic	0.9077	pathogenic	-1.459	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
K/D	0.9985	likely_pathogenic	0.9988	pathogenic	-2.121	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
K/E	0.9474	likely_pathogenic	0.957	pathogenic	-1.79	Destabilizing	0.982	D	0.725	prob.delet.	D	0.522238509	None	None	N
K/F	0.979	likely_pathogenic	0.9798	pathogenic	-0.599	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
K/G	0.9857	likely_pathogenic	0.9871	pathogenic	-1.937	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
K/H	0.8391	likely_pathogenic	0.8582	pathogenic	-1.7	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
K/I	0.8517	likely_pathogenic	0.8805	pathogenic	0.04	Stabilizing	0.975	D	0.853	deleterious	N	0.470177016	None	None	N
K/L	0.8571	likely_pathogenic	0.8699	pathogenic	0.04	Stabilizing	0.962	D	0.791	deleterious	None	None	None	None	N
K/M	0.727	likely_pathogenic	0.7522	pathogenic	-0.324	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/N	0.9916	likely_pathogenic	0.9931	pathogenic	-1.935	Destabilizing	0.998	D	0.819	deleterious	D	0.522238509	None	None	N
K/P	0.9993	likely_pathogenic	0.9994	pathogenic	-0.43	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
K/Q	0.6254	likely_pathogenic	0.6646	pathogenic	-1.512	Destabilizing	0.987	D	0.819	deleterious	N	0.497550889	None	None	N
K/R	0.1196	likely_benign	0.1206	benign	-0.931	Destabilizing	0.198	N	0.39	neutral	N	0.495180655	None	None	N
K/S	0.9817	likely_pathogenic	0.9843	pathogenic	-2.447	Highly Destabilizing	0.996	D	0.753	deleterious	None	None	None	None	N
K/T	0.8896	likely_pathogenic	0.9145	pathogenic	-1.845	Destabilizing	0.995	D	0.79	deleterious	N	0.502866807	None	None	N
K/V	0.815	likely_pathogenic	0.8457	pathogenic	-0.43	Destabilizing	0.985	D	0.825	deleterious	None	None	None	None	N
K/W	0.9674	likely_pathogenic	0.9727	pathogenic	-0.68	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/Y	0.9346	likely_pathogenic	0.9384	pathogenic	-0.335	Destabilizing	0.996	D	0.853	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.