TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5674	17245;17246;17247	chr2:178731855;178731854;178731853	chr2:179596582;179596581;179596580
N2AB	5357	16294;16295;16296	chr2:178731855;178731854;178731853	chr2:179596582;179596581;179596580
N2A	4430	13513;13514;13515	chr2:178731855;178731854;178731853	chr2:179596582;179596581;179596580
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-40
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.9835
• 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
N/K	rs1373550135	0.47	0.27	N	0.303	0.113	0.0716867268079	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
N/K	rs1373550135	0.47	0.27	N	0.303	0.113	0.0716867268079	gnomAD-4.0.0	4.77403E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.29824E-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
N/A	0.2084	likely_benign	0.1914	benign	-0.308	Destabilizing	0.013	N	0.191	neutral	None	None	None	None	I
N/C	0.3368	likely_benign	0.3169	benign	0.28	Stabilizing	0.995	D	0.376	neutral	None	None	None	None	I
N/D	0.0976	likely_benign	0.0936	benign	0.295	Stabilizing	0.006	N	0.142	neutral	N	0.420247674	None	None	I
N/E	0.2954	likely_benign	0.2766	benign	0.264	Stabilizing	0.329	N	0.331	neutral	None	None	None	None	I
N/F	0.5894	likely_pathogenic	0.5675	pathogenic	-0.73	Destabilizing	0.981	D	0.4	neutral	None	None	None	None	I
N/G	0.188	likely_benign	0.1775	benign	-0.469	Destabilizing	0.329	N	0.315	neutral	None	None	None	None	I
N/H	0.107	likely_benign	0.1051	benign	-0.434	Destabilizing	0.927	D	0.341	neutral	N	0.47645046	None	None	I
N/I	0.3396	likely_benign	0.3378	benign	0.024	Stabilizing	0.927	D	0.452	neutral	N	0.495652296	None	None	I
N/K	0.1987	likely_benign	0.1849	benign	0.175	Stabilizing	0.27	N	0.303	neutral	N	0.390215555	None	None	I
N/L	0.3353	likely_benign	0.3212	benign	0.024	Stabilizing	0.704	D	0.437	neutral	None	None	None	None	I
N/M	0.3841	ambiguous	0.3743	ambiguous	0.221	Stabilizing	0.981	D	0.371	neutral	None	None	None	None	I
N/P	0.7327	likely_pathogenic	0.6941	pathogenic	-0.06	Destabilizing	0.828	D	0.45	neutral	None	None	None	None	I
N/Q	0.2471	likely_benign	0.2347	benign	-0.236	Destabilizing	0.085	N	0.159	neutral	None	None	None	None	I
N/R	0.2371	likely_benign	0.2177	benign	0.225	Stabilizing	0.704	D	0.363	neutral	None	None	None	None	I
N/S	0.0848	likely_benign	0.0817	benign	-0.075	Destabilizing	0.01	N	0.125	neutral	N	0.418863594	None	None	I
N/T	0.1543	likely_benign	0.1471	benign	0.041	Stabilizing	0.27	N	0.301	neutral	N	0.464982673	None	None	I
N/V	0.3371	likely_benign	0.332	benign	-0.06	Destabilizing	0.704	D	0.453	neutral	None	None	None	None	I
N/W	0.7986	likely_pathogenic	0.7809	pathogenic	-0.742	Destabilizing	0.995	D	0.434	neutral	None	None	None	None	I
N/Y	0.2265	likely_benign	0.2164	benign	-0.454	Destabilizing	0.975	D	0.396	neutral	N	0.495478938	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.