TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16461	49606;49607;49608	chr2:178613902;178613901;178613900	chr2:179478629;179478628;179478627
N2AB	14820	44683;44684;44685	chr2:178613902;178613901;178613900	chr2:179478629;179478628;179478627
N2A	13893	41902;41903;41904	chr2:178613902;178613901;178613900	chr2:179478629;179478628;179478627
N2B	7396	22411;22412;22413	chr2:178613902;178613901;178613900	chr2:179478629;179478628;179478627
Novex-1	7521	22786;22787;22788	chr2:178613902;178613901;178613900	chr2:179478629;179478628;179478627
Novex-2	7588	22987;22988;22989	chr2:178613902;178613901;178613900	chr2:179478629;179478628;179478627
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-7
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.5399
• 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
D/G	None	None	0.977	D	0.639	0.402	0.328752806141	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.6594	likely_pathogenic	0.6818	pathogenic	-0.306	Destabilizing	0.977	D	0.589	neutral	N	0.513737898	None	None	N
D/C	0.9359	likely_pathogenic	0.9414	pathogenic	0.152	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
D/E	0.4694	ambiguous	0.4575	ambiguous	-0.259	Destabilizing	0.117	N	0.183	neutral	N	0.477744999	None	None	N
D/F	0.935	likely_pathogenic	0.9351	pathogenic	-0.321	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
D/G	0.694	likely_pathogenic	0.7157	pathogenic	-0.49	Destabilizing	0.977	D	0.639	neutral	D	0.557379031	None	None	N
D/H	0.8464	likely_pathogenic	0.8515	pathogenic	-0.218	Destabilizing	0.999	D	0.649	neutral	D	0.599846784	None	None	N
D/I	0.8881	likely_pathogenic	0.8961	pathogenic	0.128	Stabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
D/K	0.9101	likely_pathogenic	0.9244	pathogenic	0.446	Stabilizing	0.99	D	0.67	neutral	None	None	None	None	N
D/L	0.8603	likely_pathogenic	0.8646	pathogenic	0.128	Stabilizing	0.995	D	0.684	prob.neutral	None	None	None	None	N
D/M	0.9355	likely_pathogenic	0.9386	pathogenic	0.337	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
D/N	0.3586	ambiguous	0.3997	ambiguous	0.147	Stabilizing	0.993	D	0.644	neutral	N	0.47947139	None	None	N
D/P	0.9908	likely_pathogenic	0.9926	pathogenic	0.005	Stabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
D/Q	0.845	likely_pathogenic	0.8552	pathogenic	0.167	Stabilizing	0.99	D	0.707	prob.neutral	None	None	None	None	N
D/R	0.9156	likely_pathogenic	0.9255	pathogenic	0.52	Stabilizing	0.995	D	0.645	neutral	None	None	None	None	N
D/S	0.5145	ambiguous	0.5593	ambiguous	0.05	Stabilizing	0.983	D	0.595	neutral	None	None	None	None	N
D/T	0.7568	likely_pathogenic	0.7786	pathogenic	0.196	Stabilizing	0.995	D	0.655	neutral	None	None	None	None	N
D/V	0.758	likely_pathogenic	0.7757	pathogenic	0.005	Stabilizing	0.997	D	0.688	prob.neutral	D	0.590297234	None	None	N
D/W	0.9877	likely_pathogenic	0.9876	pathogenic	-0.198	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
D/Y	0.7461	likely_pathogenic	0.7573	pathogenic	-0.081	Destabilizing	1.0	D	0.653	neutral	D	0.632412624	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.