TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7124	21595;21596;21597	chr2:178723889;178723888;178723887	chr2:179588616;179588615;179588614
N2AB	6807	20644;20645;20646	chr2:178723889;178723888;178723887	chr2:179588616;179588615;179588614
N2A	5880	17863;17864;17865	chr2:178723889;178723888;178723887	chr2:179588616;179588615;179588614
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-55
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.5671
• Predicted PPI site: I

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/T	None	None	0.01	N	0.112	0.208	0.162503812791	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.1081	likely_benign	0.1012	benign	-0.416	Destabilizing	0.01	N	0.125	neutral	D	0.522399833	None	None	I
S/C	0.2197	likely_benign	0.1958	benign	-0.341	Destabilizing	0.013	N	0.283	neutral	D	0.535325195	None	None	I
S/D	0.4378	ambiguous	0.3833	ambiguous	-0.114	Destabilizing	0.704	D	0.287	neutral	None	None	None	None	I
S/E	0.4791	ambiguous	0.4091	ambiguous	-0.205	Destabilizing	0.543	D	0.263	neutral	None	None	None	None	I
S/F	0.2196	likely_benign	0.1782	benign	-0.935	Destabilizing	0.975	D	0.578	neutral	N	0.504547961	None	None	I
S/G	0.1374	likely_benign	0.1311	benign	-0.545	Destabilizing	0.329	N	0.293	neutral	None	None	None	None	I
S/H	0.349	ambiguous	0.2763	benign	-1.054	Destabilizing	0.981	D	0.499	neutral	None	None	None	None	I
S/I	0.2301	likely_benign	0.1886	benign	-0.205	Destabilizing	0.704	D	0.537	neutral	None	None	None	None	I
S/K	0.5494	ambiguous	0.4476	ambiguous	-0.637	Destabilizing	0.007	N	0.147	neutral	None	None	None	None	I
S/L	0.1363	likely_benign	0.1197	benign	-0.205	Destabilizing	0.495	N	0.537	neutral	None	None	None	None	I
S/M	0.2439	likely_benign	0.2241	benign	0.089	Stabilizing	0.981	D	0.501	neutral	None	None	None	None	I
S/N	0.1561	likely_benign	0.1335	benign	-0.364	Destabilizing	0.704	D	0.325	neutral	None	None	None	None	I
S/P	0.8111	likely_pathogenic	0.753	pathogenic	-0.246	Destabilizing	0.784	D	0.485	neutral	N	0.520094549	None	None	I
S/Q	0.4475	ambiguous	0.3788	ambiguous	-0.649	Destabilizing	0.893	D	0.413	neutral	None	None	None	None	I
S/R	0.4152	ambiguous	0.3213	benign	-0.373	Destabilizing	0.543	D	0.483	neutral	None	None	None	None	I
S/T	0.0994	likely_benign	0.0894	benign	-0.457	Destabilizing	0.01	N	0.112	neutral	N	0.484593594	None	None	I
S/V	0.252	likely_benign	0.2134	benign	-0.246	Destabilizing	0.704	D	0.526	neutral	None	None	None	None	I
S/W	0.3573	ambiguous	0.301	benign	-0.923	Destabilizing	0.995	D	0.596	neutral	None	None	None	None	I
S/Y	0.2094	likely_benign	0.1728	benign	-0.663	Destabilizing	0.975	D	0.567	neutral	N	0.510384085	None	None	I

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.