TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25551	76876;76877;76878	chr2:178569481;178569480;178569479	chr2:179434208;179434207;179434206
N2AB	23910	71953;71954;71955	chr2:178569481;178569480;178569479	chr2:179434208;179434207;179434206
N2A	22983	69172;69173;69174	chr2:178569481;178569480;178569479	chr2:179434208;179434207;179434206
N2B	16486	49681;49682;49683	chr2:178569481;178569480;178569479	chr2:179434208;179434207;179434206
Novex-1	16611	50056;50057;50058	chr2:178569481;178569480;178569479	chr2:179434208;179434207;179434206
Novex-2	16678	50257;50258;50259	chr2:178569481;178569480;178569479	chr2:179434208;179434207;179434206
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-135
• Domain position: 38
• Structural Position: 58
• Q(SASA): 0.1514
• 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
I/M	None	None	0.967	D	0.594	0.433	0.286465849087	gnomAD-4.0.0	1.59383E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86331E-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
I/A	0.701	likely_pathogenic	0.7506	pathogenic	-1.889	Destabilizing	0.916	D	0.511	neutral	None	None	None	None	N
I/C	0.8314	likely_pathogenic	0.8657	pathogenic	-1.445	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
I/D	0.9146	likely_pathogenic	0.9327	pathogenic	-1.236	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
I/E	0.8693	likely_pathogenic	0.8913	pathogenic	-1.126	Destabilizing	0.987	D	0.751	deleterious	None	None	None	None	N
I/F	0.2005	likely_benign	0.2196	benign	-1.081	Destabilizing	0.967	D	0.563	neutral	N	0.519151671	None	None	N
I/G	0.872	likely_pathogenic	0.9016	pathogenic	-2.292	Highly Destabilizing	0.987	D	0.745	deleterious	None	None	None	None	N
I/H	0.8368	likely_pathogenic	0.8745	pathogenic	-1.287	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
I/K	0.7897	likely_pathogenic	0.8225	pathogenic	-1.394	Destabilizing	0.987	D	0.747	deleterious	None	None	None	None	N
I/L	0.1014	likely_benign	0.1075	benign	-0.802	Destabilizing	0.011	N	0.272	neutral	N	0.427657301	None	None	N
I/M	0.1121	likely_benign	0.1169	benign	-0.909	Destabilizing	0.967	D	0.594	neutral	D	0.532715614	None	None	N
I/N	0.596	likely_pathogenic	0.6462	pathogenic	-1.453	Destabilizing	0.994	D	0.759	deleterious	N	0.509071093	None	None	N
I/P	0.7226	likely_pathogenic	0.7829	pathogenic	-1.138	Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
I/Q	0.7908	likely_pathogenic	0.8283	pathogenic	-1.441	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	N
I/R	0.7482	likely_pathogenic	0.7949	pathogenic	-0.974	Destabilizing	0.987	D	0.759	deleterious	None	None	None	None	N
I/S	0.7101	likely_pathogenic	0.7542	pathogenic	-2.149	Highly Destabilizing	0.983	D	0.652	neutral	N	0.490459859	None	None	N
I/T	0.688	likely_pathogenic	0.7307	pathogenic	-1.891	Destabilizing	0.967	D	0.623	neutral	N	0.501990294	None	None	N
I/V	0.1282	likely_benign	0.1359	benign	-1.138	Destabilizing	0.426	N	0.421	neutral	N	0.497426818	None	None	N
I/W	0.8396	likely_pathogenic	0.8654	pathogenic	-1.141	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
I/Y	0.6527	likely_pathogenic	0.7018	pathogenic	-0.94	Destabilizing	0.987	D	0.657	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.