TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25096	75511;75512;75513	chr2:178570846;178570845;178570844	chr2:179435573;179435572;179435571
N2AB	23455	70588;70589;70590	chr2:178570846;178570845;178570844	chr2:179435573;179435572;179435571
N2A	22528	67807;67808;67809	chr2:178570846;178570845;178570844	chr2:179435573;179435572;179435571
N2B	16031	48316;48317;48318	chr2:178570846;178570845;178570844	chr2:179435573;179435572;179435571
Novex-1	16156	48691;48692;48693	chr2:178570846;178570845;178570844	chr2:179435573;179435572;179435571
Novex-2	16223	48892;48893;48894	chr2:178570846;178570845;178570844	chr2:179435573;179435572;179435571
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: Fn3-70
• Domain position: 91
• Structural Position: 123
• Q(SASA): 0.3003
• 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
S/C	None	None	1.0	N	0.848	0.269	0.250039746154	gnomAD-4.0.0	1.59171E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85919E-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	0.1489	likely_benign	0.1293	benign	-1.052	Destabilizing	0.995	D	0.519	neutral	None	None	None	None	N
S/C	0.2038	likely_benign	0.1781	benign	-0.767	Destabilizing	1.0	D	0.848	deleterious	N	0.460501053	None	None	N
S/D	0.6953	likely_pathogenic	0.6559	pathogenic	-0.406	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
S/E	0.8144	likely_pathogenic	0.7769	pathogenic	-0.382	Destabilizing	0.998	D	0.784	deleterious	None	None	None	None	N
S/F	0.683	likely_pathogenic	0.6085	pathogenic	-1.167	Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
S/G	0.1604	likely_benign	0.133	benign	-1.311	Destabilizing	0.997	D	0.663	prob.neutral	N	0.484681694	None	None	N
S/H	0.7095	likely_pathogenic	0.6606	pathogenic	-1.639	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
S/I	0.3787	ambiguous	0.3124	benign	-0.453	Destabilizing	0.999	D	0.829	deleterious	N	0.465267887	None	None	N
S/K	0.9157	likely_pathogenic	0.8834	pathogenic	-0.678	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
S/L	0.298	likely_benign	0.2472	benign	-0.453	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
S/M	0.4051	ambiguous	0.3636	ambiguous	-0.193	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
S/N	0.2529	likely_benign	0.2291	benign	-0.709	Destabilizing	0.997	D	0.769	deleterious	N	0.455474623	None	None	N
S/P	0.1807	likely_benign	0.1516	benign	-0.621	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
S/Q	0.8177	likely_pathogenic	0.7723	pathogenic	-0.876	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
S/R	0.9176	likely_pathogenic	0.8789	pathogenic	-0.565	Destabilizing	0.999	D	0.839	deleterious	N	0.484174715	None	None	N
S/T	0.131	likely_benign	0.1153	benign	-0.763	Destabilizing	0.997	D	0.669	prob.neutral	N	0.456763047	None	None	N
S/V	0.3579	ambiguous	0.3031	benign	-0.621	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
S/W	0.7953	likely_pathogenic	0.7317	pathogenic	-1.07	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
S/Y	0.5871	likely_pathogenic	0.5084	ambiguous	-0.821	Destabilizing	0.999	D	0.889	deleterious	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.