TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24122	72589;72590;72591	chr2:178573768;178573767;178573766	chr2:179438495;179438494;179438493
N2AB	22481	67666;67667;67668	chr2:178573768;178573767;178573766	chr2:179438495;179438494;179438493
N2A	21554	64885;64886;64887	chr2:178573768;178573767;178573766	chr2:179438495;179438494;179438493
N2B	15057	45394;45395;45396	chr2:178573768;178573767;178573766	chr2:179438495;179438494;179438493
Novex-1	15182	45769;45770;45771	chr2:178573768;178573767;178573766	chr2:179438495;179438494;179438493
Novex-2	15249	45970;45971;45972	chr2:178573768;178573767;178573766	chr2:179438495;179438494;179438493
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-63
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.629
• 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
R/K	None	None	0.214	N	0.238	0.116	0.156986980423	gnomAD-4.0.0	1.38048E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80959E-06	0	0
R/S	None	None	0.953	N	0.657	0.253	0.218112801441	gnomAD-4.0.0	6.90221E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.04743E-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
R/A	0.6946	likely_pathogenic	0.7003	pathogenic	-0.06	Destabilizing	0.964	D	0.559	neutral	None	None	None	None	I
R/C	0.2215	likely_benign	0.244	benign	-0.156	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
R/D	0.9556	likely_pathogenic	0.9603	pathogenic	-0.081	Destabilizing	0.99	D	0.765	deleterious	None	None	None	None	I
R/E	0.7368	likely_pathogenic	0.7461	pathogenic	-0.023	Destabilizing	0.931	D	0.51	neutral	None	None	None	None	I
R/F	0.8112	likely_pathogenic	0.8034	pathogenic	-0.277	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	I
R/G	0.6594	likely_pathogenic	0.6928	pathogenic	-0.251	Destabilizing	0.953	D	0.501	neutral	N	0.491913851	None	None	I
R/H	0.2045	likely_benign	0.2283	benign	-0.699	Destabilizing	0.998	D	0.598	neutral	None	None	None	None	I
R/I	0.3562	ambiguous	0.3373	benign	0.406	Stabilizing	0.993	D	0.842	deleterious	N	0.4513997	None	None	I
R/K	0.1351	likely_benign	0.1423	benign	-0.106	Destabilizing	0.214	N	0.238	neutral	N	0.440545588	None	None	I
R/L	0.4747	ambiguous	0.4649	ambiguous	0.406	Stabilizing	0.964	D	0.501	neutral	None	None	None	None	I
R/M	0.487	ambiguous	0.4851	ambiguous	0.034	Stabilizing	1.0	D	0.57	neutral	None	None	None	None	I
R/N	0.8636	likely_pathogenic	0.8749	pathogenic	0.184	Stabilizing	0.99	D	0.599	neutral	None	None	None	None	I
R/P	0.8912	likely_pathogenic	0.9048	pathogenic	0.271	Stabilizing	0.995	D	0.849	deleterious	None	None	None	None	I
R/Q	0.1759	likely_benign	0.1834	benign	0.048	Stabilizing	0.99	D	0.642	neutral	None	None	None	None	I
R/S	0.7642	likely_pathogenic	0.7839	pathogenic	-0.198	Destabilizing	0.953	D	0.657	prob.neutral	N	0.464908826	None	None	I
R/T	0.4309	ambiguous	0.4446	ambiguous	-0.01	Destabilizing	0.993	D	0.546	neutral	N	0.50378899	None	None	I
R/V	0.4644	ambiguous	0.4474	ambiguous	0.271	Stabilizing	0.995	D	0.831	deleterious	None	None	None	None	I
R/W	0.4691	ambiguous	0.5022	ambiguous	-0.305	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
R/Y	0.6758	likely_pathogenic	0.6976	pathogenic	0.093	Stabilizing	0.998	D	0.829	deleterious	None	None	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.