TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6876	20851;20852;20853	chr2:178725578;178725577;178725576	chr2:179590305;179590304;179590303
N2AB	6559	19900;19901;19902	chr2:178725578;178725577;178725576	chr2:179590305;179590304;179590303
N2A	5632	17119;17120;17121	chr2:178725578;178725577;178725576	chr2:179590305;179590304;179590303
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-53
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1936
• 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
S/T	rs1359024577	-0.599	None	N	0.134	0.101	0.0551355673512	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
S/T	rs1359024577	-0.599	None	N	0.134	0.101	0.0551355673512	gnomAD-4.0.0	4.1089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39967E-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
S/A	0.0665	likely_benign	0.0643	benign	-0.851	Destabilizing	0.001	N	0.354	neutral	N	0.409210401	None	None	N
S/C	0.1058	likely_benign	0.1024	benign	-0.65	Destabilizing	0.196	N	0.506	neutral	N	0.494002511	None	None	N
S/D	0.2377	likely_benign	0.2253	benign	-0.254	Destabilizing	0.044	N	0.386	neutral	None	None	None	None	N
S/E	0.2526	likely_benign	0.2509	benign	-0.252	Destabilizing	0.018	N	0.367	neutral	None	None	None	None	N
S/F	0.1218	likely_benign	0.1208	benign	-1.02	Destabilizing	None	N	0.277	neutral	N	0.494002511	None	None	N
S/G	0.0979	likely_benign	0.0895	benign	-1.091	Destabilizing	0.018	N	0.377	neutral	None	None	None	None	N
S/H	0.1633	likely_benign	0.1594	benign	-1.495	Destabilizing	0.138	N	0.512	neutral	None	None	None	None	N
S/I	0.0904	likely_benign	0.0833	benign	-0.314	Destabilizing	None	N	0.255	neutral	None	None	None	None	N
S/K	0.2305	likely_benign	0.2199	benign	-0.647	Destabilizing	0.009	N	0.378	neutral	None	None	None	None	N
S/L	0.0799	likely_benign	0.0755	benign	-0.314	Destabilizing	0.004	N	0.41	neutral	None	None	None	None	N
S/M	0.1304	likely_benign	0.1289	benign	-0.066	Destabilizing	0.138	N	0.531	neutral	None	None	None	None	N
S/N	0.0844	likely_benign	0.0759	benign	-0.623	Destabilizing	0.044	N	0.4	neutral	None	None	None	None	N
S/P	0.2868	likely_benign	0.2326	benign	-0.46	Destabilizing	0.065	N	0.509	neutral	N	0.463852962	None	None	N
S/Q	0.227	likely_benign	0.2207	benign	-0.813	Destabilizing	0.044	N	0.446	neutral	None	None	None	None	N
S/R	0.1776	likely_benign	0.1733	benign	-0.528	Destabilizing	None	N	0.224	neutral	None	None	None	None	N
S/T	0.0555	likely_benign	0.0576	benign	-0.689	Destabilizing	None	N	0.134	neutral	N	0.352084894	None	None	N
S/V	0.0964	likely_benign	0.0912	benign	-0.46	Destabilizing	None	N	0.227	neutral	None	None	None	None	N
S/W	0.2249	likely_benign	0.2341	benign	-0.944	Destabilizing	0.245	N	0.563	neutral	None	None	None	None	N
S/Y	0.1158	likely_benign	0.1156	benign	-0.687	Destabilizing	None	N	0.274	neutral	N	0.493655794	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.