TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5718	17377;17378;17379	chr2:178731723;178731722;178731721	chr2:179596450;179596449;179596448
N2AB	5401	16426;16427;16428	chr2:178731723;178731722;178731721	chr2:179596450;179596449;179596448
N2A	4474	13645;13646;13647	chr2:178731723;178731722;178731721	chr2:179596450;179596449;179596448
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-40
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1113
• 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/N	None	None	0.351	N	0.407	0.153	0.165133752707	gnomAD-4.0.0	6.8467E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00045E-07	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	0.0744	likely_benign	0.0747	benign	-0.589	Destabilizing	None	N	0.097	neutral	None	None	None	None	I
S/C	0.084	likely_benign	0.0859	benign	-0.345	Destabilizing	0.001	N	0.243	neutral	N	0.44992366	None	None	I
S/D	0.3047	likely_benign	0.2807	benign	0.363	Stabilizing	0.001	N	0.18	neutral	None	None	None	None	I
S/E	0.5341	ambiguous	0.491	ambiguous	0.392	Stabilizing	0.004	N	0.168	neutral	None	None	None	None	I
S/F	0.2757	likely_benign	0.2637	benign	-0.695	Destabilizing	0.836	D	0.625	neutral	None	None	None	None	I
S/G	0.0887	likely_benign	0.096	benign	-0.861	Destabilizing	0.101	N	0.365	neutral	N	0.483420158	None	None	I
S/H	0.3779	ambiguous	0.3517	ambiguous	-1.195	Destabilizing	0.94	D	0.557	neutral	None	None	None	None	I
S/I	0.2002	likely_benign	0.1811	benign	0.032	Stabilizing	0.101	N	0.503	neutral	N	0.421294263	None	None	I
S/K	0.7125	likely_pathogenic	0.6605	pathogenic	-0.265	Destabilizing	0.228	N	0.363	neutral	None	None	None	None	I
S/L	0.148	likely_benign	0.1402	benign	0.032	Stabilizing	0.129	N	0.514	neutral	None	None	None	None	I
S/M	0.2682	likely_benign	0.2505	benign	0.031	Stabilizing	0.836	D	0.562	neutral	None	None	None	None	I
S/N	0.1395	likely_benign	0.1324	benign	-0.291	Destabilizing	0.351	N	0.407	neutral	N	0.482726724	None	None	I
S/P	0.8341	likely_pathogenic	0.8392	pathogenic	-0.14	Destabilizing	0.593	D	0.555	neutral	None	None	None	None	I
S/Q	0.5437	ambiguous	0.5003	ambiguous	-0.332	Destabilizing	0.418	N	0.466	neutral	None	None	None	None	I
S/R	0.5646	likely_pathogenic	0.519	ambiguous	-0.293	Destabilizing	0.351	N	0.575	neutral	N	0.451577098	None	None	I
S/T	0.0941	likely_benign	0.0919	benign	-0.335	Destabilizing	0.003	N	0.143	neutral	N	0.433164696	None	None	I
S/V	0.1709	likely_benign	0.1632	benign	-0.14	Destabilizing	0.004	N	0.328	neutral	None	None	None	None	I
S/W	0.4743	ambiguous	0.4488	ambiguous	-0.693	Destabilizing	0.983	D	0.61	neutral	None	None	None	None	I
S/Y	0.2244	likely_benign	0.2104	benign	-0.379	Destabilizing	0.94	D	0.623	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.