TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28390	85393;85394;85395	chr2:178560964;178560963;178560962	chr2:179425691;179425690;179425689
N2AB	26749	80470;80471;80472	chr2:178560964;178560963;178560962	chr2:179425691;179425690;179425689
N2A	25822	77689;77690;77691	chr2:178560964;178560963;178560962	chr2:179425691;179425690;179425689
N2B	19325	58198;58199;58200	chr2:178560964;178560963;178560962	chr2:179425691;179425690;179425689
Novex-1	19450	58573;58574;58575	chr2:178560964;178560963;178560962	chr2:179425691;179425690;179425689
Novex-2	19517	58774;58775;58776	chr2:178560964;178560963;178560962	chr2:179425691;179425690;179425689
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-143
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.352
• 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/F	rs267599032	None	0.994	N	0.712	0.574	0.660933345464	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
S/A	0.0903	likely_benign	0.0909	benign	-0.618	Destabilizing	0.63	D	0.435	neutral	N	0.518631596	None	None	N
S/C	0.0967	likely_benign	0.0986	benign	-0.373	Destabilizing	0.999	D	0.652	neutral	N	0.496335662	None	None	N
S/D	0.4725	ambiguous	0.4428	ambiguous	-0.132	Destabilizing	0.916	D	0.485	neutral	None	None	None	None	N
S/E	0.4777	ambiguous	0.4554	ambiguous	-0.07	Destabilizing	0.845	D	0.428	neutral	None	None	None	None	N
S/F	0.1653	likely_benign	0.1566	benign	-0.689	Destabilizing	0.994	D	0.712	prob.delet.	N	0.496488242	None	None	N
S/G	0.1434	likely_benign	0.133	benign	-0.926	Destabilizing	0.916	D	0.455	neutral	None	None	None	None	N
S/H	0.2709	likely_benign	0.2633	benign	-1.322	Destabilizing	0.997	D	0.664	neutral	None	None	None	None	N
S/I	0.1376	likely_benign	0.1366	benign	0.108	Stabilizing	0.987	D	0.691	prob.neutral	None	None	None	None	N
S/K	0.5918	likely_pathogenic	0.5723	pathogenic	-0.419	Destabilizing	0.033	N	0.385	neutral	None	None	None	None	N
S/L	0.0918	likely_benign	0.0898	benign	0.108	Stabilizing	0.916	D	0.626	neutral	None	None	None	None	N
S/M	0.1817	likely_benign	0.174	benign	0.15	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	N
S/N	0.1769	likely_benign	0.1642	benign	-0.595	Destabilizing	0.916	D	0.491	neutral	None	None	None	None	N
S/P	0.9327	likely_pathogenic	0.9253	pathogenic	-0.097	Destabilizing	0.983	D	0.651	neutral	N	0.513932938	None	None	N
S/Q	0.4374	ambiguous	0.4163	ambiguous	-0.568	Destabilizing	0.975	D	0.565	neutral	None	None	None	None	N
S/R	0.4934	ambiguous	0.4676	ambiguous	-0.492	Destabilizing	0.95	D	0.604	neutral	None	None	None	None	N
S/T	0.0738	likely_benign	0.0741	benign	-0.52	Destabilizing	0.892	D	0.441	neutral	N	0.419718183	None	None	N
S/V	0.1475	likely_benign	0.1477	benign	-0.097	Destabilizing	0.975	D	0.606	neutral	None	None	None	None	N
S/W	0.3141	likely_benign	0.2882	benign	-0.76	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
S/Y	0.152	likely_benign	0.1462	benign	-0.418	Destabilizing	0.994	D	0.71	prob.delet.	N	0.496082172	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.