TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35784	107575;107576;107577	chr2:178528301;178528300;178528299	chr2:179393028;179393027;179393026
N2AB	34143	102652;102653;102654	chr2:178528301;178528300;178528299	chr2:179393028;179393027;179393026
N2A	33216	99871;99872;99873	chr2:178528301;178528300;178528299	chr2:179393028;179393027;179393026
N2B	26719	80380;80381;80382	chr2:178528301;178528300;178528299	chr2:179393028;179393027;179393026
Novex-1	26844	80755;80756;80757	chr2:178528301;178528300;178528299	chr2:179393028;179393027;179393026
Novex-2	26911	80956;80957;80958	chr2:178528301;178528300;178528299	chr2:179393028;179393027;179393026
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-168
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.4839
• 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/P	None	None	0.997	N	0.663	0.647	0.435043484731	gnomAD-4.0.0	1.59114E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88267E-05	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	0.1282	likely_benign	0.1169	benign	-0.471	Destabilizing	0.4	N	0.205	neutral	N	0.489531125	None	None	I
S/C	0.3074	likely_benign	0.2776	benign	-0.323	Destabilizing	0.323	N	0.44	neutral	None	None	None	None	I
S/D	0.8203	likely_pathogenic	0.7626	pathogenic	0.328	Stabilizing	0.998	D	0.509	neutral	None	None	None	None	I
S/E	0.7615	likely_pathogenic	0.6904	pathogenic	0.276	Stabilizing	0.993	D	0.488	neutral	None	None	None	None	I
S/F	0.3227	likely_benign	0.2698	benign	-0.899	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
S/G	0.2885	likely_benign	0.27	benign	-0.643	Destabilizing	0.985	D	0.476	neutral	None	None	None	None	I
S/H	0.617	likely_pathogenic	0.5516	ambiguous	-1.057	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
S/I	0.3127	likely_benign	0.2541	benign	-0.141	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	I
S/K	0.9155	likely_pathogenic	0.8782	pathogenic	-0.448	Destabilizing	0.993	D	0.481	neutral	None	None	None	None	I
S/L	0.1702	likely_benign	0.1456	benign	-0.141	Destabilizing	0.98	D	0.591	neutral	N	0.48922841	None	None	I
S/M	0.3443	ambiguous	0.2913	benign	-0.06	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
S/N	0.3715	ambiguous	0.3183	benign	-0.248	Destabilizing	0.999	D	0.525	neutral	None	None	None	None	I
S/P	0.9285	likely_pathogenic	0.9167	pathogenic	-0.219	Destabilizing	0.997	D	0.663	neutral	N	0.520259133	None	None	I
S/Q	0.7309	likely_pathogenic	0.6761	pathogenic	-0.4	Destabilizing	0.999	D	0.537	neutral	None	None	None	None	I
S/R	0.8608	likely_pathogenic	0.8128	pathogenic	-0.303	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	I
S/T	0.1151	likely_benign	0.0983	benign	-0.328	Destabilizing	0.98	D	0.475	neutral	N	0.461617946	None	None	I
S/V	0.3128	likely_benign	0.2563	benign	-0.219	Destabilizing	0.985	D	0.605	neutral	None	None	None	None	I
S/W	0.6219	likely_pathogenic	0.5576	ambiguous	-0.91	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
S/Y	0.3656	ambiguous	0.3014	benign	-0.623	Destabilizing	0.999	D	0.717	prob.delet.	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.