TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24658	74197;74198;74199	chr2:178572160;178572159;178572158	chr2:179436887;179436886;179436885
N2AB	23017	69274;69275;69276	chr2:178572160;178572159;178572158	chr2:179436887;179436886;179436885
N2A	22090	66493;66494;66495	chr2:178572160;178572159;178572158	chr2:179436887;179436886;179436885
N2B	15593	47002;47003;47004	chr2:178572160;178572159;178572158	chr2:179436887;179436886;179436885
Novex-1	15718	47377;47378;47379	chr2:178572160;178572159;178572158	chr2:179436887;179436886;179436885
Novex-2	15785	47578;47579;47580	chr2:178572160;178572159;178572158	chr2:179436887;179436886;179436885
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: Fn3-67
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.571
• 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/E	None	None	0.032	N	0.279	0.209	0.224531998449	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85927E-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	0.5099	ambiguous	0.4586	ambiguous	0.049	Stabilizing	0.979	D	0.578	neutral	None	None	None	None	N
K/C	0.8892	likely_pathogenic	0.8772	pathogenic	-0.224	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
K/D	0.8339	likely_pathogenic	0.8071	pathogenic	0.075	Stabilizing	0.959	D	0.614	neutral	None	None	None	None	N
K/E	0.424	ambiguous	0.379	ambiguous	0.068	Stabilizing	0.032	N	0.279	neutral	N	0.504338856	None	None	N
K/F	0.9511	likely_pathogenic	0.9343	pathogenic	-0.243	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
K/G	0.6953	likely_pathogenic	0.6511	pathogenic	-0.12	Destabilizing	0.994	D	0.621	neutral	None	None	None	None	N
K/H	0.5604	ambiguous	0.5223	ambiguous	-0.391	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	N
K/I	0.6737	likely_pathogenic	0.6125	pathogenic	0.408	Stabilizing	0.88	D	0.699	prob.neutral	N	0.470914712	None	None	N
K/L	0.6808	likely_pathogenic	0.6273	pathogenic	0.408	Stabilizing	0.828	D	0.633	neutral	None	None	None	None	N
K/M	0.5608	ambiguous	0.5022	ambiguous	0.216	Stabilizing	0.998	D	0.617	neutral	None	None	None	None	N
K/N	0.7478	likely_pathogenic	0.699	pathogenic	0.264	Stabilizing	0.992	D	0.627	neutral	N	0.475460616	None	None	N
K/P	0.77	likely_pathogenic	0.7408	pathogenic	0.315	Stabilizing	0.997	D	0.665	neutral	None	None	None	None	N
K/Q	0.2627	likely_benign	0.2342	benign	0.075	Stabilizing	0.882	D	0.61	neutral	N	0.492866854	None	None	N
K/R	0.0894	likely_benign	0.0869	benign	0.016	Stabilizing	0.867	D	0.529	neutral	N	0.478903656	None	None	N
K/S	0.6809	likely_pathogenic	0.6259	pathogenic	-0.208	Destabilizing	0.979	D	0.589	neutral	None	None	None	None	N
K/T	0.4584	ambiguous	0.4019	ambiguous	-0.076	Destabilizing	0.974	D	0.62	neutral	N	0.51016875	None	None	N
K/V	0.575	likely_pathogenic	0.5222	ambiguous	0.315	Stabilizing	0.928	D	0.691	prob.neutral	None	None	None	None	N
K/W	0.937	likely_pathogenic	0.9235	pathogenic	-0.274	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
K/Y	0.8905	likely_pathogenic	0.8672	pathogenic	0.096	Stabilizing	0.979	D	0.671	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.