TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32150	96673;96674;96675	chr2:178543525;178543524;178543523	chr2:179408252;179408251;179408250
N2AB	30509	91750;91751;91752	chr2:178543525;178543524;178543523	chr2:179408252;179408251;179408250
N2A	29582	88969;88970;88971	chr2:178543525;178543524;178543523	chr2:179408252;179408251;179408250
N2B	23085	69478;69479;69480	chr2:178543525;178543524;178543523	chr2:179408252;179408251;179408250
Novex-1	23210	69853;69854;69855	chr2:178543525;178543524;178543523	chr2:179408252;179408251;179408250
Novex-2	23277	70054;70055;70056	chr2:178543525;178543524;178543523	chr2:179408252;179408251;179408250
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: Fn3-122
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9432
• 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
R/T	None	None	0.98	N	0.53	0.316	0.336155897331	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.8591	likely_pathogenic	0.8208	pathogenic	-0.045	Destabilizing	0.931	D	0.483	neutral	None	None	None	None	N
R/C	0.6648	likely_pathogenic	0.5563	ambiguous	-0.34	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	N
R/D	0.9681	likely_pathogenic	0.9594	pathogenic	-0.395	Destabilizing	0.996	D	0.503	neutral	None	None	None	None	N
R/E	0.8578	likely_pathogenic	0.8292	pathogenic	-0.373	Destabilizing	0.97	D	0.516	neutral	None	None	None	None	N
R/F	0.9203	likely_pathogenic	0.8944	pathogenic	-0.399	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
R/G	0.7813	likely_pathogenic	0.6943	pathogenic	-0.143	Destabilizing	0.98	D	0.497	neutral	N	0.428971518	None	None	N
R/H	0.3958	ambiguous	0.3088	benign	-0.602	Destabilizing	0.999	D	0.576	neutral	None	None	None	None	N
R/I	0.79	likely_pathogenic	0.7249	pathogenic	0.169	Stabilizing	0.998	D	0.588	neutral	N	0.494564579	None	None	N
R/K	0.2074	likely_benign	0.1731	benign	-0.288	Destabilizing	0.122	N	0.2	neutral	N	0.411273979	None	None	N
R/L	0.6195	likely_pathogenic	0.5458	ambiguous	0.169	Stabilizing	0.985	D	0.497	neutral	None	None	None	None	N
R/M	0.7177	likely_pathogenic	0.6492	pathogenic	-0.203	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	N
R/N	0.9416	likely_pathogenic	0.92	pathogenic	-0.2	Destabilizing	0.985	D	0.52	neutral	None	None	None	None	N
R/P	0.8962	likely_pathogenic	0.832	pathogenic	0.113	Stabilizing	0.999	D	0.562	neutral	None	None	None	None	N
R/Q	0.3614	ambiguous	0.2884	benign	-0.224	Destabilizing	0.97	D	0.519	neutral	None	None	None	None	N
R/S	0.9406	likely_pathogenic	0.9153	pathogenic	-0.33	Destabilizing	0.961	D	0.508	neutral	N	0.446482631	None	None	N
R/T	0.8349	likely_pathogenic	0.7715	pathogenic	-0.224	Destabilizing	0.98	D	0.53	neutral	N	0.466415186	None	None	N
R/V	0.8119	likely_pathogenic	0.7557	pathogenic	0.113	Stabilizing	0.996	D	0.535	neutral	None	None	None	None	N
R/W	0.614	likely_pathogenic	0.5134	ambiguous	-0.621	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
R/Y	0.8147	likely_pathogenic	0.7594	pathogenic	-0.244	Destabilizing	0.999	D	0.582	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.