TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6808	20647;20648;20649	chr2:178725900;178725899;178725898	chr2:179590627;179590626;179590625
N2AB	6491	19696;19697;19698	chr2:178725900;178725899;178725898	chr2:179590627;179590626;179590625
N2A	5564	16915;16916;16917	chr2:178725900;178725899;178725898	chr2:179590627;179590626;179590625
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-52
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.5282
• 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
K/T	None	None	0.864	N	0.537	0.332	0.42069145522	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	6.07533E-05	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
K/A	0.9022	likely_pathogenic	0.9071	pathogenic	-0.789	Destabilizing	0.92	D	0.529	neutral	None	None	None	None	N
K/C	0.947	likely_pathogenic	0.9563	pathogenic	-0.873	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/D	0.9664	likely_pathogenic	0.9648	pathogenic	-0.393	Destabilizing	0.982	D	0.526	neutral	None	None	None	None	N
K/E	0.7503	likely_pathogenic	0.7687	pathogenic	-0.258	Destabilizing	0.927	D	0.525	neutral	N	0.512337555	None	None	N
K/F	0.9606	likely_pathogenic	0.9678	pathogenic	-0.483	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
K/G	0.9441	likely_pathogenic	0.9466	pathogenic	-1.178	Destabilizing	0.149	N	0.282	neutral	None	None	None	None	N
K/H	0.6262	likely_pathogenic	0.6486	pathogenic	-1.543	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
K/I	0.7331	likely_pathogenic	0.781	pathogenic	0.233	Stabilizing	0.921	D	0.632	neutral	None	None	None	None	N
K/L	0.7544	likely_pathogenic	0.7816	pathogenic	0.233	Stabilizing	0.77	D	0.513	neutral	None	None	None	None	N
K/M	0.6522	likely_pathogenic	0.6937	pathogenic	0.175	Stabilizing	0.998	D	0.592	neutral	N	0.512790395	None	None	N
K/N	0.9108	likely_pathogenic	0.9074	pathogenic	-0.722	Destabilizing	0.977	D	0.497	neutral	N	0.48721372	None	None	N
K/P	0.9927	likely_pathogenic	0.991	pathogenic	-0.078	Destabilizing	0.997	D	0.579	neutral	None	None	None	None	N
K/Q	0.4012	ambiguous	0.4119	ambiguous	-0.786	Destabilizing	0.973	D	0.539	neutral	N	0.493117076	None	None	N
K/R	0.1142	likely_benign	0.1133	benign	-0.739	Destabilizing	0.195	N	0.213	neutral	N	0.486305747	None	None	N
K/S	0.9051	likely_pathogenic	0.9114	pathogenic	-1.425	Destabilizing	0.686	D	0.227	neutral	None	None	None	None	N
K/T	0.6641	likely_pathogenic	0.6939	pathogenic	-1.069	Destabilizing	0.864	D	0.537	neutral	N	0.496677456	None	None	N
K/V	0.7253	likely_pathogenic	0.7602	pathogenic	-0.078	Destabilizing	0.939	D	0.535	neutral	None	None	None	None	N
K/W	0.9377	likely_pathogenic	0.9512	pathogenic	-0.344	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/Y	0.8905	likely_pathogenic	0.9104	pathogenic	-0.023	Destabilizing	0.983	D	0.624	neutral	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.