TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9446	28561;28562;28563	chr2:178710761;178710760;178710759	chr2:179575488;179575487;179575486
N2AB	9129	27610;27611;27612	chr2:178710761;178710760;178710759	chr2:179575488;179575487;179575486
N2A	8202	24829;24830;24831	chr2:178710761;178710760;178710759	chr2:179575488;179575487;179575486
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-80
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.4671
• 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	rs762605364	None	0.939	None	0.491	0.323	0.475818030638	gnomAD-4.0.0	2.05249E-06	None	None	None	None	I	None	0	0	None	0	2.51902E-05	None	0	0	8.99423E-07	0	1.6564E-05
S/T	None	None	0.079	None	0.188	0.146	0.304760801415	gnomAD-4.0.0	6.84163E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.6564E-05

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	0.0997	likely_benign	0.1219	benign	-0.501	Destabilizing	0.807	D	0.348	neutral	None	None	None	None	I
S/C	0.1705	likely_benign	0.2943	benign	-0.268	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
S/D	0.3784	ambiguous	0.5447	ambiguous	-0.072	Destabilizing	0.953	D	0.47	neutral	None	None	None	None	I
S/E	0.4781	ambiguous	0.6792	pathogenic	-0.095	Destabilizing	0.953	D	0.481	neutral	None	None	None	None	I
S/F	0.2066	likely_benign	0.3024	benign	-0.683	Destabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	I
S/G	0.1221	likely_benign	0.1781	benign	-0.734	Destabilizing	0.939	D	0.422	neutral	None	None	None	None	I
S/H	0.2538	likely_benign	0.4573	ambiguous	-1.202	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
S/I	0.1813	likely_benign	0.294	benign	0.001	Stabilizing	0.982	D	0.702	prob.neutral	None	None	None	None	I
S/K	0.5116	ambiguous	0.786	pathogenic	-0.721	Destabilizing	0.953	D	0.474	neutral	None	None	None	None	I
S/L	0.135	likely_benign	0.1837	benign	0.001	Stabilizing	0.91	D	0.557	neutral	None	None	None	None	I
S/M	0.252	likely_benign	0.3703	ambiguous	0.166	Stabilizing	0.999	D	0.628	neutral	None	None	None	None	I
S/N	0.1436	likely_benign	0.2277	benign	-0.523	Destabilizing	0.939	D	0.491	neutral	None	None	None	None	I
S/P	0.7641	likely_pathogenic	0.9282	pathogenic	-0.132	Destabilizing	0.993	D	0.657	neutral	None	None	None	None	I
S/Q	0.4105	ambiguous	0.6382	pathogenic	-0.647	Destabilizing	0.993	D	0.587	neutral	None	None	None	None	I
S/R	0.3581	ambiguous	0.6383	pathogenic	-0.594	Destabilizing	0.991	D	0.667	neutral	None	None	None	None	I
S/T	0.0713	likely_benign	0.087	benign	-0.532	Destabilizing	0.079	N	0.188	neutral	None	None	None	None	I
S/V	0.2063	likely_benign	0.3015	benign	-0.132	Destabilizing	0.91	D	0.546	neutral	None	None	None	None	I
S/W	0.3128	likely_benign	0.506	ambiguous	-0.719	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	I
S/Y	0.1691	likely_benign	0.2844	benign	-0.461	Destabilizing	0.998	D	0.702	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.