TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19354	58285;58286;58287	chr2:178594434;178594433;178594432	chr2:179459161;179459160;179459159
N2AB	17713	53362;53363;53364	chr2:178594434;178594433;178594432	chr2:179459161;179459160;179459159
N2A	16786	50581;50582;50583	chr2:178594434;178594433;178594432	chr2:179459161;179459160;179459159
N2B	10289	31090;31091;31092	chr2:178594434;178594433;178594432	chr2:179459161;179459160;179459159
Novex-1	10414	31465;31466;31467	chr2:178594434;178594433;178594432	chr2:179459161;179459160;179459159
Novex-2	10481	31666;31667;31668	chr2:178594434;178594433;178594432	chr2:179459161;179459160;179459159
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-28
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.1505
• 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
T/N	None	None	0.961	N	0.442	0.259	0.328486982098	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
T/A	0.1411	likely_benign	0.1379	benign	-0.994	Destabilizing	0.835	D	0.308	neutral	N	0.501722625	None	None	N
T/C	0.5128	ambiguous	0.5353	ambiguous	-0.57	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
T/D	0.7577	likely_pathogenic	0.7188	pathogenic	-0.735	Destabilizing	0.97	D	0.563	neutral	None	None	None	None	N
T/E	0.6283	likely_pathogenic	0.5731	pathogenic	-0.611	Destabilizing	0.97	D	0.556	neutral	None	None	None	None	N
T/F	0.5705	likely_pathogenic	0.536	ambiguous	-0.736	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
T/G	0.5107	ambiguous	0.4885	ambiguous	-1.367	Destabilizing	0.97	D	0.581	neutral	None	None	None	None	N
T/H	0.5191	ambiguous	0.4944	ambiguous	-1.561	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
T/I	0.2683	likely_benign	0.2503	benign	-0.049	Destabilizing	0.994	D	0.641	neutral	N	0.515788	None	None	N
T/K	0.5057	ambiguous	0.4311	ambiguous	-0.597	Destabilizing	0.97	D	0.555	neutral	None	None	None	None	N
T/L	0.2468	likely_benign	0.2253	benign	-0.049	Destabilizing	0.985	D	0.515	neutral	None	None	None	None	N
T/M	0.154	likely_benign	0.1503	benign	0.042	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
T/N	0.2447	likely_benign	0.237	benign	-0.947	Destabilizing	0.961	D	0.442	neutral	N	0.476978896	None	None	N
T/P	0.5843	likely_pathogenic	0.5189	ambiguous	-0.331	Destabilizing	0.994	D	0.645	neutral	N	0.466026413	None	None	N
T/Q	0.4164	ambiguous	0.3835	ambiguous	-0.862	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	N
T/R	0.4546	ambiguous	0.3843	ambiguous	-0.653	Destabilizing	0.996	D	0.678	prob.neutral	None	None	None	None	N
T/S	0.1634	likely_benign	0.1675	benign	-1.217	Destabilizing	0.287	N	0.213	neutral	N	0.42110697	None	None	N
T/V	0.2048	likely_benign	0.1948	benign	-0.331	Destabilizing	0.985	D	0.399	neutral	None	None	None	None	N
T/W	0.8621	likely_pathogenic	0.8431	pathogenic	-0.799	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/Y	0.5345	ambiguous	0.5126	ambiguous	-0.48	Destabilizing	0.999	D	0.787	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.