TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23369	70330;70331;70332	chr2:178576027;178576026;178576025	chr2:179440754;179440753;179440752
N2AB	21728	65407;65408;65409	chr2:178576027;178576026;178576025	chr2:179440754;179440753;179440752
N2A	20801	62626;62627;62628	chr2:178576027;178576026;178576025	chr2:179440754;179440753;179440752
N2B	14304	43135;43136;43137	chr2:178576027;178576026;178576025	chr2:179440754;179440753;179440752
Novex-1	14429	43510;43511;43512	chr2:178576027;178576026;178576025	chr2:179440754;179440753;179440752
Novex-2	14496	43711;43712;43713	chr2:178576027;178576026;178576025	chr2:179440754;179440753;179440752
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-129
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.8066
• 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
K/E	rs1277463353	None	0.822	N	0.541	0.179	0.332386209738	gnomAD-4.0.0	1.59238E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86071E-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
K/A	0.4862	ambiguous	0.6136	pathogenic	-0.042	Destabilizing	0.86	D	0.56	neutral	None	None	None	None	I
K/C	0.683	likely_pathogenic	0.7783	pathogenic	-0.613	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	I
K/D	0.8496	likely_pathogenic	0.9123	pathogenic	-0.277	Destabilizing	0.978	D	0.586	neutral	None	None	None	None	I
K/E	0.3836	ambiguous	0.5004	ambiguous	-0.29	Destabilizing	0.822	D	0.541	neutral	N	0.481801218	None	None	I
K/F	0.8451	likely_pathogenic	0.9076	pathogenic	-0.417	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	I
K/G	0.6838	likely_pathogenic	0.7864	pathogenic	-0.151	Destabilizing	0.956	D	0.49	neutral	None	None	None	None	I
K/H	0.312	likely_benign	0.3802	ambiguous	-0.207	Destabilizing	0.994	D	0.582	neutral	None	None	None	None	I
K/I	0.4582	ambiguous	0.5896	pathogenic	0.16	Stabilizing	0.971	D	0.612	neutral	N	0.493751795	None	None	I
K/L	0.5318	ambiguous	0.6426	pathogenic	0.16	Stabilizing	0.956	D	0.49	neutral	None	None	None	None	I
K/M	0.3518	ambiguous	0.448	ambiguous	-0.205	Destabilizing	0.998	D	0.574	neutral	None	None	None	None	I
K/N	0.6646	likely_pathogenic	0.7736	pathogenic	-0.159	Destabilizing	0.942	D	0.573	neutral	D	0.535406416	None	None	I
K/P	0.9775	likely_pathogenic	0.9866	pathogenic	0.115	Stabilizing	0.993	D	0.585	neutral	None	None	None	None	I
K/Q	0.176	likely_benign	0.217	benign	-0.274	Destabilizing	0.942	D	0.576	neutral	N	0.452193174	None	None	I
K/R	0.0764	likely_benign	0.0828	benign	-0.185	Destabilizing	0.006	N	0.263	neutral	N	0.449768944	None	None	I
K/S	0.5348	ambiguous	0.6599	pathogenic	-0.519	Destabilizing	0.86	D	0.541	neutral	None	None	None	None	I
K/T	0.218	likely_benign	0.2938	benign	-0.42	Destabilizing	0.942	D	0.547	neutral	N	0.457348277	None	None	I
K/V	0.4132	ambiguous	0.5311	ambiguous	0.115	Stabilizing	0.978	D	0.584	neutral	None	None	None	None	I
K/W	0.7948	likely_pathogenic	0.871	pathogenic	-0.53	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	I
K/Y	0.7315	likely_pathogenic	0.8249	pathogenic	-0.178	Destabilizing	0.993	D	0.584	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.