TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18930	57013;57014;57015	chr2:178598922;178598921;178598920	chr2:179463649;179463648;179463647
N2AB	17289	52090;52091;52092	chr2:178598922;178598921;178598920	chr2:179463649;179463648;179463647
N2A	16362	49309;49310;49311	chr2:178598922;178598921;178598920	chr2:179463649;179463648;179463647
N2B	9865	29818;29819;29820	chr2:178598922;178598921;178598920	chr2:179463649;179463648;179463647
Novex-1	9990	30193;30194;30195	chr2:178598922;178598921;178598920	chr2:179463649;179463648;179463647
Novex-2	10057	30394;30395;30396	chr2:178598922;178598921;178598920	chr2:179463649;179463648;179463647
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: Fn3-25
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.7693
• 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	rs727503595	None	1.0	N	0.587	0.312	0.284150004643	gnomAD-4.0.0	6.84471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99651E-06	0	0
R/K	rs746833235	0.097	0.997	N	0.591	0.279	0.350964488264	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	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	0.8963	likely_pathogenic	0.8518	pathogenic	0.1	Stabilizing	0.999	D	0.593	neutral	None	None	None	None	N
R/C	0.6128	likely_pathogenic	0.56	ambiguous	-0.17	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
R/D	0.9602	likely_pathogenic	0.9489	pathogenic	-0.192	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
R/E	0.8886	likely_pathogenic	0.8402	pathogenic	-0.134	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
R/F	0.8631	likely_pathogenic	0.8279	pathogenic	-0.163	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
R/G	0.7991	likely_pathogenic	0.7449	pathogenic	-0.071	Destabilizing	1.0	D	0.587	neutral	N	0.48867597	None	None	N
R/H	0.3341	likely_benign	0.2699	benign	-0.6	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
R/I	0.6857	likely_pathogenic	0.5786	pathogenic	0.507	Stabilizing	1.0	D	0.737	prob.delet.	N	0.470154244	None	None	N
R/K	0.2912	likely_benign	0.2456	benign	-0.053	Destabilizing	0.997	D	0.591	neutral	N	0.494044504	None	None	N
R/L	0.6368	likely_pathogenic	0.5832	pathogenic	0.507	Stabilizing	1.0	D	0.587	neutral	None	None	None	None	N
R/M	0.7369	likely_pathogenic	0.6703	pathogenic	-0.008	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
R/N	0.9059	likely_pathogenic	0.8722	pathogenic	0.047	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
R/P	0.9671	likely_pathogenic	0.9571	pathogenic	0.391	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
R/Q	0.3682	ambiguous	0.3011	benign	0.014	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
R/S	0.9259	likely_pathogenic	0.9001	pathogenic	-0.169	Destabilizing	1.0	D	0.613	neutral	N	0.48959869	None	None	N
R/T	0.8225	likely_pathogenic	0.7273	pathogenic	0.011	Stabilizing	1.0	D	0.625	neutral	N	0.488542684	None	None	N
R/V	0.7781	likely_pathogenic	0.7	pathogenic	0.391	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
R/W	0.5072	ambiguous	0.4484	ambiguous	-0.314	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
R/Y	0.6976	likely_pathogenic	0.6311	pathogenic	0.104	Stabilizing	1.0	D	0.703	prob.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.