TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31153	93682;93683;93684	chr2:178548169;178548168;178548167	chr2:179412896;179412895;179412894
N2AB	29512	88759;88760;88761	chr2:178548169;178548168;178548167	chr2:179412896;179412895;179412894
N2A	28585	85978;85979;85980	chr2:178548169;178548168;178548167	chr2:179412896;179412895;179412894
N2B	22088	66487;66488;66489	chr2:178548169;178548168;178548167	chr2:179412896;179412895;179412894
Novex-1	22213	66862;66863;66864	chr2:178548169;178548168;178548167	chr2:179412896;179412895;179412894
Novex-2	22280	67063;67064;67065	chr2:178548169;178548168;178548167	chr2:179412896;179412895;179412894
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: Fn3-115
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.3505
• 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
R/G	None	None	0.896	N	0.601	0.383	0.465721554213	gnomAD-4.0.0	6.8417E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99439E-07	0	0
R/K	None	None	0.011	N	0.115	0.124	0.252162846088	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
R/A	0.7957	likely_pathogenic	0.6348	pathogenic	-2.187	Highly Destabilizing	0.825	D	0.546	neutral	None	None	None	None	N
R/C	0.2515	likely_benign	0.1666	benign	-2.119	Highly Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
R/D	0.9806	likely_pathogenic	0.954	pathogenic	-0.903	Destabilizing	0.976	D	0.664	neutral	None	None	None	None	N
R/E	0.7623	likely_pathogenic	0.6104	pathogenic	-0.715	Destabilizing	0.851	D	0.465	neutral	None	None	None	None	N
R/F	0.8754	likely_pathogenic	0.7474	pathogenic	-1.613	Destabilizing	0.996	D	0.757	deleterious	None	None	None	None	N
R/G	0.7236	likely_pathogenic	0.5156	ambiguous	-2.493	Highly Destabilizing	0.896	D	0.601	neutral	N	0.482639866	None	None	N
R/H	0.2637	likely_benign	0.183	benign	-2.38	Highly Destabilizing	0.996	D	0.52	neutral	None	None	None	None	N
R/I	0.644	likely_pathogenic	0.4565	ambiguous	-1.302	Destabilizing	0.984	D	0.751	deleterious	N	0.493742682	None	None	N
R/K	0.1057	likely_benign	0.0791	benign	-1.573	Destabilizing	0.011	N	0.115	neutral	N	0.462857592	None	None	N
R/L	0.5006	ambiguous	0.3063	benign	-1.302	Destabilizing	0.919	D	0.601	neutral	None	None	None	None	N
R/M	0.5275	ambiguous	0.3443	ambiguous	-1.746	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
R/N	0.9188	likely_pathogenic	0.847	pathogenic	-1.286	Destabilizing	0.919	D	0.479	neutral	None	None	None	None	N
R/P	0.9892	likely_pathogenic	0.9702	pathogenic	-1.587	Destabilizing	0.988	D	0.702	prob.neutral	None	None	None	None	N
R/Q	0.1418	likely_benign	0.111	benign	-1.303	Destabilizing	0.919	D	0.513	neutral	None	None	None	None	N
R/S	0.8902	likely_pathogenic	0.7731	pathogenic	-2.279	Highly Destabilizing	0.896	D	0.545	neutral	N	0.502530701	None	None	N
R/T	0.7875	likely_pathogenic	0.5963	pathogenic	-1.896	Destabilizing	0.896	D	0.58	neutral	N	0.479664125	None	None	N
R/V	0.7187	likely_pathogenic	0.5527	ambiguous	-1.587	Destabilizing	0.988	D	0.664	neutral	None	None	None	None	N
R/W	0.5943	likely_pathogenic	0.3859	ambiguous	-1.08	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
R/Y	0.7764	likely_pathogenic	0.6262	pathogenic	-0.937	Destabilizing	0.996	D	0.741	deleterious	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.