TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34215	102868;102869;102870	chr2:178533972;178533971;178533970	chr2:179398699;179398698;179398697
N2AB	32574	97945;97946;97947	chr2:178533972;178533971;178533970	chr2:179398699;179398698;179398697
N2A	31647	95164;95165;95166	chr2:178533972;178533971;178533970	chr2:179398699;179398698;179398697
N2B	25150	75673;75674;75675	chr2:178533972;178533971;178533970	chr2:179398699;179398698;179398697
Novex-1	25275	76048;76049;76050	chr2:178533972;178533971;178533970	chr2:179398699;179398698;179398697
Novex-2	25342	76249;76250;76251	chr2:178533972;178533971;178533970	chr2:179398699;179398698;179398697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-160
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.9595
• 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
Y/C	rs2154135557	None	0.999	N	0.569	0.569	0.600692567571	gnomAD-4.0.0	3.18211E-06	None	None	None	None	N	None	0	0	None	0	5.54539E-05	None	0	0	0	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
Y/A	0.6038	likely_pathogenic	0.5636	ambiguous	-0.339	Destabilizing	0.148	N	0.398	neutral	None	None	None	None	N
Y/C	0.3594	ambiguous	0.384	ambiguous	0.28	Stabilizing	0.999	D	0.569	neutral	N	0.487365078	None	None	N
Y/D	0.3903	ambiguous	0.351	ambiguous	0.806	Stabilizing	0.068	N	0.427	neutral	N	0.506603662	None	None	N
Y/E	0.7255	likely_pathogenic	0.7011	pathogenic	0.769	Stabilizing	0.939	D	0.555	neutral	None	None	None	None	N
Y/F	0.1229	likely_benign	0.121	benign	-0.234	Destabilizing	0.993	D	0.449	neutral	N	0.465813045	None	None	N
Y/G	0.6445	likely_pathogenic	0.5918	pathogenic	-0.494	Destabilizing	0.927	D	0.561	neutral	None	None	None	None	N
Y/H	0.3119	likely_benign	0.2953	benign	0.364	Stabilizing	0.994	D	0.447	neutral	N	0.479225059	None	None	N
Y/I	0.6771	likely_pathogenic	0.65	pathogenic	0.025	Stabilizing	0.995	D	0.537	neutral	None	None	None	None	N
Y/K	0.7316	likely_pathogenic	0.6787	pathogenic	0.379	Stabilizing	0.969	D	0.579	neutral	None	None	None	None	N
Y/L	0.588	likely_pathogenic	0.5525	ambiguous	0.025	Stabilizing	0.969	D	0.511	neutral	None	None	None	None	N
Y/M	0.7188	likely_pathogenic	0.69	pathogenic	0.057	Stabilizing	0.999	D	0.555	neutral	None	None	None	None	N
Y/N	0.2793	likely_benign	0.2534	benign	0.195	Stabilizing	0.238	N	0.42	neutral	N	0.479225059	None	None	N
Y/P	0.9839	likely_pathogenic	0.9788	pathogenic	-0.076	Destabilizing	0.995	D	0.554	neutral	None	None	None	None	N
Y/Q	0.6902	likely_pathogenic	0.6537	pathogenic	0.235	Stabilizing	0.995	D	0.551	neutral	None	None	None	None	N
Y/R	0.5568	ambiguous	0.4988	ambiguous	0.556	Stabilizing	0.995	D	0.572	neutral	None	None	None	None	N
Y/S	0.3119	likely_benign	0.2889	benign	-0.136	Destabilizing	0.828	D	0.562	neutral	N	0.480262422	None	None	N
Y/T	0.6273	likely_pathogenic	0.5861	pathogenic	-0.083	Destabilizing	0.969	D	0.583	neutral	None	None	None	None	N
Y/V	0.5418	ambiguous	0.5105	ambiguous	-0.076	Destabilizing	0.969	D	0.548	neutral	None	None	None	None	N
Y/W	0.5784	likely_pathogenic	0.5695	pathogenic	-0.473	Destabilizing	1.0	D	0.469	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.