TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33456	100591;100592;100593	chr2:178536381;178536380;178536379	chr2:179401108;179401107;179401106
N2AB	31815	95668;95669;95670	chr2:178536381;178536380;178536379	chr2:179401108;179401107;179401106
N2A	30888	92887;92888;92889	chr2:178536381;178536380;178536379	chr2:179401108;179401107;179401106
N2B	24391	73396;73397;73398	chr2:178536381;178536380;178536379	chr2:179401108;179401107;179401106
Novex-1	24516	73771;73772;73773	chr2:178536381;178536380;178536379	chr2:179401108;179401107;179401106
Novex-2	24583	73972;73973;73974	chr2:178536381;178536380;178536379	chr2:179401108;179401107;179401106
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-131
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.7926
• 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
N/S	None	None	0.625	N	0.356	0.178	0.148003135375	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/Y	None	None	0.989	N	0.427	0.404	0.541149246611	gnomAD-4.0.0	1.59152E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02425E-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
N/A	0.2831	likely_benign	0.2352	benign	-0.139	Destabilizing	0.525	D	0.366	neutral	None	None	None	None	I
N/C	0.3644	ambiguous	0.2899	benign	0.264	Stabilizing	0.998	D	0.467	neutral	None	None	None	None	I
N/D	0.1136	likely_benign	0.1034	benign	0.183	Stabilizing	0.012	N	0.142	neutral	N	0.415661078	None	None	I
N/E	0.3341	likely_benign	0.3122	benign	0.131	Stabilizing	0.728	D	0.321	neutral	None	None	None	None	I
N/F	0.6506	likely_pathogenic	0.5637	ambiguous	-0.658	Destabilizing	0.991	D	0.464	neutral	None	None	None	None	I
N/G	0.2108	likely_benign	0.1655	benign	-0.262	Destabilizing	0.002	N	0.115	neutral	None	None	None	None	I
N/H	0.1363	likely_benign	0.125	benign	-0.263	Destabilizing	0.989	D	0.388	neutral	N	0.491759134	None	None	I
N/I	0.4289	ambiguous	0.3665	ambiguous	0.09	Stabilizing	0.966	D	0.469	neutral	N	0.490655263	None	None	I
N/K	0.3105	likely_benign	0.3075	benign	0.144	Stabilizing	0.801	D	0.345	neutral	N	0.415933224	None	None	I
N/L	0.3909	ambiguous	0.3329	benign	0.09	Stabilizing	0.974	D	0.475	neutral	None	None	None	None	I
N/M	0.4557	ambiguous	0.3767	ambiguous	0.197	Stabilizing	0.998	D	0.412	neutral	None	None	None	None	I
N/P	0.7941	likely_pathogenic	0.7833	pathogenic	0.038	Stabilizing	0.974	D	0.44	neutral	None	None	None	None	I
N/Q	0.3193	likely_benign	0.2892	benign	-0.208	Destabilizing	0.974	D	0.387	neutral	None	None	None	None	I
N/R	0.4178	ambiguous	0.3895	ambiguous	0.21	Stabilizing	0.974	D	0.379	neutral	None	None	None	None	I
N/S	0.1111	likely_benign	0.0978	benign	-0.002	Destabilizing	0.625	D	0.356	neutral	N	0.482099501	None	None	I
N/T	0.179	likely_benign	0.1479	benign	0.07	Stabilizing	0.891	D	0.323	neutral	D	0.523716837	None	None	I
N/V	0.4171	ambiguous	0.3531	ambiguous	0.038	Stabilizing	0.974	D	0.471	neutral	None	None	None	None	I
N/W	0.8121	likely_pathogenic	0.758	pathogenic	-0.749	Destabilizing	0.998	D	0.566	neutral	None	None	None	None	I
N/Y	0.1981	likely_benign	0.1745	benign	-0.438	Destabilizing	0.989	D	0.427	neutral	N	0.478880884	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.