TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7074	21445;21446;21447	chr2:178724039;178724038;178724037	chr2:179588766;179588765;179588764
N2AB	6757	20494;20495;20496	chr2:178724039;178724038;178724037	chr2:179588766;179588765;179588764
N2A	5830	17713;17714;17715	chr2:178724039;178724038;178724037	chr2:179588766;179588765;179588764
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: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-55
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4668
• 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/L	rs1456194529	0.195	0.811	D	0.545	0.292	0.738737919071	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	1.14705E-04	0	None	0	0	None	0	None	0	0	0
S/L	rs1456194529	0.195	0.811	D	0.545	0.292	0.738737919071	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/L	rs1456194529	0.195	0.811	D	0.545	0.292	0.738737919071	gnomAD-4.0.0	6.57125E-06	None	None	None	None	I	None	2.41138E-05	0	None	0	0	None	0	0	0	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	0.1061	likely_benign	0.0991	benign	-0.428	Destabilizing	0.64	D	0.321	neutral	D	0.526749647	None	None	I
S/C	0.2296	likely_benign	0.2445	benign	-0.444	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	I
S/D	0.4453	ambiguous	0.4274	ambiguous	0.243	Stabilizing	0.919	D	0.409	neutral	None	None	None	None	I
S/E	0.5198	ambiguous	0.5226	ambiguous	0.22	Stabilizing	0.919	D	0.398	neutral	None	None	None	None	I
S/F	0.2443	likely_benign	0.2129	benign	-0.905	Destabilizing	0.988	D	0.689	prob.neutral	None	None	None	None	I
S/G	0.1993	likely_benign	0.1798	benign	-0.609	Destabilizing	0.919	D	0.4	neutral	None	None	None	None	I
S/H	0.3897	ambiguous	0.3879	ambiguous	-0.958	Destabilizing	0.999	D	0.612	neutral	None	None	None	None	I
S/I	0.267	likely_benign	0.2403	benign	-0.07	Destabilizing	0.976	D	0.609	neutral	None	None	None	None	I
S/K	0.6873	likely_pathogenic	0.6973	pathogenic	-0.381	Destabilizing	0.919	D	0.408	neutral	None	None	None	None	I
S/L	0.1335	likely_benign	0.1184	benign	-0.07	Destabilizing	0.811	D	0.545	neutral	D	0.529328593	None	None	I
S/M	0.2819	likely_benign	0.2621	benign	-0.158	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	I
S/N	0.2328	likely_benign	0.211	benign	-0.365	Destabilizing	0.919	D	0.411	neutral	None	None	None	None	I
S/P	0.7232	likely_pathogenic	0.7202	pathogenic	-0.158	Destabilizing	0.984	D	0.579	neutral	D	0.527869683	None	None	I
S/Q	0.546	ambiguous	0.5577	ambiguous	-0.432	Destabilizing	0.988	D	0.526	neutral	None	None	None	None	I
S/R	0.5719	likely_pathogenic	0.579	pathogenic	-0.272	Destabilizing	0.976	D	0.583	neutral	None	None	None	None	I
S/T	0.0885	likely_benign	0.0859	benign	-0.377	Destabilizing	0.016	N	0.161	neutral	N	0.472280444	None	None	I
S/V	0.2458	likely_benign	0.2204	benign	-0.158	Destabilizing	0.851	D	0.543	neutral	None	None	None	None	I
S/W	0.4245	ambiguous	0.379	ambiguous	-0.974	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
S/Y	0.2225	likely_benign	0.2009	benign	-0.639	Destabilizing	0.996	D	0.691	prob.neutral	None	None	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.