TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31809	95650;95651;95652	chr2:178545685;178545684;178545683	chr2:179410412;179410411;179410410
N2AB	30168	90727;90728;90729	chr2:178545685;178545684;178545683	chr2:179410412;179410411;179410410
N2A	29241	87946;87947;87948	chr2:178545685;178545684;178545683	chr2:179410412;179410411;179410410
N2B	22744	68455;68456;68457	chr2:178545685;178545684;178545683	chr2:179410412;179410411;179410410
Novex-1	22869	68830;68831;68832	chr2:178545685;178545684;178545683	chr2:179410412;179410411;179410410
Novex-2	22936	69031;69032;69033	chr2:178545685;178545684;178545683	chr2:179410412;179410411;179410410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-120
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2743
• 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	0.984	N	0.593	0.393	0.32580497728	gnomAD-4.0.0	3.42417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.50105E-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	0.0962	likely_benign	0.0964	benign	-0.677	Destabilizing	0.64	D	0.533	neutral	D	0.523426049	None	None	N
S/C	0.142	likely_benign	0.1399	benign	-0.621	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
S/D	0.366	ambiguous	0.371	ambiguous	-0.916	Destabilizing	0.851	D	0.616	neutral	None	None	None	None	N
S/E	0.5821	likely_pathogenic	0.5998	pathogenic	-0.903	Destabilizing	0.919	D	0.627	neutral	None	None	None	None	N
S/F	0.2285	likely_benign	0.2377	benign	-0.855	Destabilizing	0.988	D	0.622	neutral	None	None	None	None	N
S/G	0.0826	likely_benign	0.0782	benign	-0.934	Destabilizing	0.919	D	0.58	neutral	None	None	None	None	N
S/H	0.4272	ambiguous	0.4414	ambiguous	-1.477	Destabilizing	0.997	D	0.613	neutral	None	None	None	None	N
S/I	0.3321	likely_benign	0.3503	ambiguous	-0.095	Destabilizing	0.976	D	0.593	neutral	None	None	None	None	N
S/K	0.7468	likely_pathogenic	0.7618	pathogenic	-0.812	Destabilizing	0.919	D	0.623	neutral	None	None	None	None	N
S/L	0.0943	likely_benign	0.0947	benign	-0.095	Destabilizing	0.811	D	0.553	neutral	N	0.492728723	None	None	N
S/M	0.2189	likely_benign	0.2253	benign	0.223	Stabilizing	0.999	D	0.609	neutral	None	None	None	None	N
S/N	0.1744	likely_benign	0.1786	benign	-0.895	Destabilizing	0.132	N	0.413	neutral	None	None	None	None	N
S/P	0.7155	likely_pathogenic	0.7426	pathogenic	-0.255	Destabilizing	0.984	D	0.593	neutral	N	0.503831539	None	None	N
S/Q	0.5847	likely_pathogenic	0.6062	pathogenic	-1.081	Destabilizing	0.988	D	0.624	neutral	None	None	None	None	N
S/R	0.7367	likely_pathogenic	0.7494	pathogenic	-0.701	Destabilizing	0.988	D	0.588	neutral	None	None	None	None	N
S/T	0.0869	likely_benign	0.0888	benign	-0.811	Destabilizing	0.046	N	0.24	neutral	N	0.518404231	None	None	N
S/V	0.2786	likely_benign	0.3017	benign	-0.255	Destabilizing	0.851	D	0.521	neutral	None	None	None	None	N
S/W	0.493	ambiguous	0.4936	ambiguous	-0.875	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
S/Y	0.2455	likely_benign	0.2541	benign	-0.579	Destabilizing	0.996	D	0.623	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.