TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35648	107167;107168;107169	chr2:178528809;178528808;178528807	chr2:179393536;179393535;179393534
N2AB	34007	102244;102245;102246	chr2:178528809;178528808;178528807	chr2:179393536;179393535;179393534
N2A	33080	99463;99464;99465	chr2:178528809;178528808;178528807	chr2:179393536;179393535;179393534
N2B	26583	79972;79973;79974	chr2:178528809;178528808;178528807	chr2:179393536;179393535;179393534
Novex-1	26708	80347;80348;80349	chr2:178528809;178528808;178528807	chr2:179393536;179393535;179393534
Novex-2	26775	80548;80549;80550	chr2:178528809;178528808;178528807	chr2:179393536;179393535;179393534
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-167
• Domain position: 42
• Structural Position: 73
• Q(SASA): 0.1675
• 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
S/P	None	None	1.0	N	0.719	0.52	0.278968121808	gnomAD-4.0.0	2.05272E-06	None	None	None	None	N	None	0	0	None	0	5.03931E-05	None	0	0	8.99493E-07	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
S/A	0.1762	likely_benign	0.1651	benign	-0.656	Destabilizing	0.997	D	0.468	neutral	N	0.465158818	None	None	N
S/C	0.2969	likely_benign	0.2546	benign	-0.337	Destabilizing	1.0	D	0.723	prob.delet.	N	0.466372326	None	None	N
S/D	0.578	likely_pathogenic	0.5597	ambiguous	0.235	Stabilizing	0.999	D	0.618	neutral	None	None	None	None	N
S/E	0.8228	likely_pathogenic	0.8018	pathogenic	0.215	Stabilizing	0.999	D	0.605	neutral	None	None	None	None	N
S/F	0.6763	likely_pathogenic	0.6305	pathogenic	-0.891	Destabilizing	1.0	D	0.75	deleterious	N	0.466198968	None	None	N
S/G	0.1649	likely_benign	0.1458	benign	-0.885	Destabilizing	0.999	D	0.522	neutral	None	None	None	None	N
S/H	0.6616	likely_pathogenic	0.6071	pathogenic	-1.328	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
S/I	0.6462	likely_pathogenic	0.5899	pathogenic	-0.161	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
S/K	0.8949	likely_pathogenic	0.8774	pathogenic	-0.548	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
S/L	0.3079	likely_benign	0.2646	benign	-0.161	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
S/M	0.533	ambiguous	0.4625	ambiguous	0.064	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
S/N	0.2789	likely_benign	0.2628	benign	-0.408	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
S/P	0.8981	likely_pathogenic	0.8998	pathogenic	-0.292	Destabilizing	1.0	D	0.719	prob.delet.	N	0.465678893	None	None	N
S/Q	0.807	likely_pathogenic	0.7754	pathogenic	-0.538	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
S/R	0.8372	likely_pathogenic	0.8244	pathogenic	-0.467	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
S/T	0.1253	likely_benign	0.1095	benign	-0.488	Destabilizing	0.999	D	0.486	neutral	N	0.464638743	None	None	N
S/V	0.6013	likely_pathogenic	0.5384	ambiguous	-0.292	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
S/W	0.7642	likely_pathogenic	0.7338	pathogenic	-0.865	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
S/Y	0.5805	likely_pathogenic	0.5406	ambiguous	-0.604	Destabilizing	1.0	D	0.752	deleterious	N	0.466198968	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.