TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22145	66658;66659;66660	chr2:178581936;178581935;178581934	chr2:179446663;179446662;179446661
N2AB	20504	61735;61736;61737	chr2:178581936;178581935;178581934	chr2:179446663;179446662;179446661
N2A	19577	58954;58955;58956	chr2:178581936;178581935;178581934	chr2:179446663;179446662;179446661
N2B	13080	39463;39464;39465	chr2:178581936;178581935;178581934	chr2:179446663;179446662;179446661
Novex-1	13205	39838;39839;39840	chr2:178581936;178581935;178581934	chr2:179446663;179446662;179446661
Novex-2	13272	40039;40040;40041	chr2:178581936;178581935;178581934	chr2:179446663;179446662;179446661
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: Fn3-48
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.2721
• 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/P	None	None	0.999	N	0.839	0.461	0.36453787251	gnomAD-4.0.0	1.5926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86043E-06	0	0
S/Y	None	None	0.999	N	0.861	0.443	0.600100745787	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	0.4806	ambiguous	0.5072	ambiguous	-0.64	Destabilizing	0.994	D	0.664	prob.neutral	N	0.485479659	None	None	N
S/C	0.5192	ambiguous	0.5588	ambiguous	-0.471	Destabilizing	1.0	D	0.783	deleterious	N	0.493686094	None	None	N
S/D	0.9898	likely_pathogenic	0.9902	pathogenic	-0.667	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
S/E	0.9952	likely_pathogenic	0.996	pathogenic	-0.58	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
S/F	0.9915	likely_pathogenic	0.9926	pathogenic	-0.457	Destabilizing	0.999	D	0.868	deleterious	N	0.506497203	None	None	N
S/G	0.4596	ambiguous	0.4733	ambiguous	-0.985	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
S/H	0.9914	likely_pathogenic	0.9925	pathogenic	-1.394	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
S/I	0.9788	likely_pathogenic	0.9774	pathogenic	0.195	Stabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
S/K	0.9992	likely_pathogenic	0.9993	pathogenic	-0.67	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
S/L	0.9089	likely_pathogenic	0.9174	pathogenic	0.195	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
S/M	0.9467	likely_pathogenic	0.9479	pathogenic	0.228	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
S/N	0.962	likely_pathogenic	0.9645	pathogenic	-0.885	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
S/P	0.991	likely_pathogenic	0.9918	pathogenic	-0.047	Destabilizing	0.999	D	0.839	deleterious	N	0.514005621	None	None	N
S/Q	0.9928	likely_pathogenic	0.9937	pathogenic	-0.836	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
S/R	0.9985	likely_pathogenic	0.9987	pathogenic	-0.766	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
S/T	0.2795	likely_benign	0.2727	benign	-0.739	Destabilizing	0.997	D	0.748	deleterious	N	0.51657186	None	None	N
S/V	0.9307	likely_pathogenic	0.9284	pathogenic	-0.047	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
S/W	0.994	likely_pathogenic	0.9949	pathogenic	-0.575	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
S/Y	0.9915	likely_pathogenic	0.9925	pathogenic	-0.242	Destabilizing	0.999	D	0.861	deleterious	N	0.513498642	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.