TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10142	30649;30650;30651	chr2:178702463;178702462;178702461	chr2:179567190;179567189;179567188
N2AB	9825	29698;29699;29700	chr2:178702463;178702462;178702461	chr2:179567190;179567189;179567188
N2A	8898	26917;26918;26919	chr2:178702463;178702462;178702461	chr2:179567190;179567189;179567188
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-86
• Domain position: 65
• Structural Position: 148
• Q(SASA): 0.7859
• 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/N	rs1577675584	None	0.896	None	0.439	0.24	0.201204373187	gnomAD-4.0.0	2.73666E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99395E-07	0	4.96919E-05
D/Y	None	None	0.995	None	0.481	0.275	0.332133492242	gnomAD-4.0.0	2.05249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69819E-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	0.3817	ambiguous	0.3327	benign	-0.003	Destabilizing	0.103	N	0.251	neutral	None	None	None	None	N
D/C	0.963	likely_pathogenic	0.9618	pathogenic	0.163	Stabilizing	0.999	D	0.498	neutral	None	None	None	None	N
D/E	0.2801	likely_benign	0.2299	benign	-0.198	Destabilizing	0.028	N	0.166	neutral	None	None	None	None	N
D/F	0.9359	likely_pathogenic	0.923	pathogenic	-0.193	Destabilizing	0.996	D	0.481	neutral	None	None	None	None	N
D/G	0.5059	ambiguous	0.4612	ambiguous	-0.122	Destabilizing	0.811	D	0.419	neutral	None	None	None	None	N
D/H	0.793	likely_pathogenic	0.717	pathogenic	0.215	Stabilizing	0.984	D	0.392	neutral	None	None	None	None	N
D/I	0.861	likely_pathogenic	0.8396	pathogenic	0.241	Stabilizing	0.988	D	0.488	neutral	None	None	None	None	N
D/K	0.7894	likely_pathogenic	0.6913	pathogenic	0.514	Stabilizing	0.851	D	0.425	neutral	None	None	None	None	N
D/L	0.8049	likely_pathogenic	0.7706	pathogenic	0.241	Stabilizing	0.976	D	0.431	neutral	None	None	None	None	N
D/M	0.9225	likely_pathogenic	0.8968	pathogenic	0.238	Stabilizing	0.999	D	0.47	neutral	None	None	None	None	N
D/N	0.2937	likely_benign	0.2445	benign	0.409	Stabilizing	0.896	D	0.439	neutral	None	None	None	None	N
D/P	0.9821	likely_pathogenic	0.9811	pathogenic	0.18	Stabilizing	0.988	D	0.385	neutral	None	None	None	None	N
D/Q	0.7132	likely_pathogenic	0.5627	ambiguous	0.396	Stabilizing	0.851	D	0.389	neutral	None	None	None	None	N
D/R	0.834	likely_pathogenic	0.7517	pathogenic	0.64	Stabilizing	0.976	D	0.429	neutral	None	None	None	None	N
D/S	0.3181	likely_benign	0.2628	benign	0.288	Stabilizing	0.851	D	0.398	neutral	None	None	None	None	N
D/T	0.6437	likely_pathogenic	0.598	pathogenic	0.377	Stabilizing	0.919	D	0.442	neutral	None	None	None	None	N
D/V	0.6805	likely_pathogenic	0.6425	pathogenic	0.18	Stabilizing	0.896	D	0.449	neutral	None	None	None	None	N
D/W	0.988	likely_pathogenic	0.986	pathogenic	-0.175	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
D/Y	0.7136	likely_pathogenic	0.6742	pathogenic	0.027	Stabilizing	0.995	D	0.481	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.