TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30545	91858;91859;91860	chr2:178550205;178550204;178550203	chr2:179414932;179414931;179414930
N2AB	28904	86935;86936;86937	chr2:178550205;178550204;178550203	chr2:179414932;179414931;179414930
N2A	27977	84154;84155;84156	chr2:178550205;178550204;178550203	chr2:179414932;179414931;179414930
N2B	21480	64663;64664;64665	chr2:178550205;178550204;178550203	chr2:179414932;179414931;179414930
Novex-1	21605	65038;65039;65040	chr2:178550205;178550204;178550203	chr2:179414932;179414931;179414930
Novex-2	21672	65239;65240;65241	chr2:178550205;178550204;178550203	chr2:179414932;179414931;179414930
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-149
• Domain position: 14
• Structural Position: 29
• Q(SASA): 0.4865
• 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
R/K	None	None	0.011	N	0.271	0.106	0.104622674875	gnomAD-4.0.0	1.20038E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31256E-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
R/A	0.5789	likely_pathogenic	0.6231	pathogenic	-0.627	Destabilizing	0.851	D	0.597	neutral	None	None	None	None	I
R/C	0.2114	likely_benign	0.2341	benign	-0.717	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	I
R/D	0.828	likely_pathogenic	0.8513	pathogenic	0.097	Stabilizing	0.976	D	0.613	neutral	None	None	None	None	I
R/E	0.5274	ambiguous	0.5669	pathogenic	0.241	Stabilizing	0.851	D	0.587	neutral	None	None	None	None	I
R/F	0.6783	likely_pathogenic	0.7076	pathogenic	-0.422	Destabilizing	0.988	D	0.666	neutral	None	None	None	None	I
R/G	0.4837	ambiguous	0.5285	ambiguous	-0.931	Destabilizing	0.896	D	0.58	neutral	N	0.508866017	None	None	I
R/H	0.1207	likely_benign	0.1326	benign	-1.204	Destabilizing	0.988	D	0.614	neutral	None	None	None	None	I
R/I	0.3677	ambiguous	0.3942	ambiguous	0.185	Stabilizing	0.938	D	0.654	neutral	N	0.460096206	None	None	I
R/K	0.1179	likely_benign	0.1319	benign	-0.492	Destabilizing	0.011	N	0.271	neutral	N	0.474639519	None	None	I
R/L	0.3394	likely_benign	0.3677	ambiguous	0.185	Stabilizing	0.851	D	0.6	neutral	None	None	None	None	I
R/M	0.3902	ambiguous	0.4221	ambiguous	-0.36	Destabilizing	0.702	D	0.483	neutral	None	None	None	None	I
R/N	0.6992	likely_pathogenic	0.7427	pathogenic	-0.25	Destabilizing	0.976	D	0.585	neutral	None	None	None	None	I
R/P	0.8949	likely_pathogenic	0.9105	pathogenic	-0.065	Destabilizing	0.988	D	0.648	neutral	None	None	None	None	I
R/Q	0.1286	likely_benign	0.1456	benign	-0.297	Destabilizing	0.919	D	0.606	neutral	None	None	None	None	I
R/S	0.6421	likely_pathogenic	0.6898	pathogenic	-0.947	Destabilizing	0.896	D	0.563	neutral	N	0.509368168	None	None	I
R/T	0.3708	ambiguous	0.4093	ambiguous	-0.612	Destabilizing	0.896	D	0.585	neutral	N	0.488739393	None	None	I
R/V	0.4275	ambiguous	0.4616	ambiguous	-0.065	Destabilizing	0.851	D	0.597	neutral	None	None	None	None	I
R/W	0.2591	likely_benign	0.2743	benign	-0.168	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
R/Y	0.4869	ambiguous	0.5222	ambiguous	0.13	Stabilizing	0.996	D	0.649	neutral	None	None	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.