TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30719	92380;92381;92382	chr2:178549471;178549470;178549469	chr2:179414198;179414197;179414196
N2AB	29078	87457;87458;87459	chr2:178549471;178549470;178549469	chr2:179414198;179414197;179414196
N2A	28151	84676;84677;84678	chr2:178549471;178549470;178549469	chr2:179414198;179414197;179414196
N2B	21654	65185;65186;65187	chr2:178549471;178549470;178549469	chr2:179414198;179414197;179414196
Novex-1	21779	65560;65561;65562	chr2:178549471;178549470;178549469	chr2:179414198;179414197;179414196
Novex-2	21846	65761;65762;65763	chr2:178549471;178549470;178549469	chr2:179414198;179414197;179414196
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-112
• Domain position: 1
• Structural Position: 1
• Q(SASA): 1.2601
• 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
V/D	None	None	0.314	N	0.737	0.249	0.73976330059	gnomAD-4.0.0	1.62473E-06	None	None	None	None	I	None	0	0	None	0	2.79018E-05	None	0	0	0	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
V/A	0.178	likely_benign	0.1647	benign	-0.829	Destabilizing	0.026	N	0.601	neutral	N	0.484883516	None	None	I
V/C	0.7083	likely_pathogenic	0.6944	pathogenic	-0.682	Destabilizing	0.934	D	0.653	prob.neutral	None	None	None	None	I
V/D	0.5808	likely_pathogenic	0.5329	ambiguous	-0.665	Destabilizing	0.314	N	0.737	deleterious	N	0.499726482	None	None	I
V/E	0.3945	ambiguous	0.3397	benign	-0.78	Destabilizing	0.378	N	0.734	deleterious	None	None	None	None	I
V/F	0.2615	likely_benign	0.2523	benign	-1.083	Destabilizing	0.314	N	0.661	prob.neutral	N	0.517830737	None	None	I
V/G	0.3412	ambiguous	0.3283	benign	-0.98	Destabilizing	0.314	N	0.657	prob.neutral	N	0.517830737	None	None	I
V/H	0.6036	likely_pathogenic	0.5783	pathogenic	-0.521	Destabilizing	0.934	D	0.762	deleterious	None	None	None	None	I
V/I	0.0755	likely_benign	0.0763	benign	-0.572	Destabilizing	None	N	0.279	neutral	N	0.472214477	None	None	I
V/K	0.2967	likely_benign	0.2656	benign	-0.527	Destabilizing	0.378	N	0.725	deleterious	None	None	None	None	I
V/L	0.1608	likely_benign	0.1715	benign	-0.572	Destabilizing	None	N	0.314	neutral	N	0.511302113	None	None	I
V/M	0.1442	likely_benign	0.149	benign	-0.355	Destabilizing	0.378	N	0.515	neutral	None	None	None	None	I
V/N	0.3519	ambiguous	0.3388	benign	-0.252	Destabilizing	0.378	N	0.721	deleterious	None	None	None	None	I
V/P	0.3256	likely_benign	0.2921	benign	-0.623	Destabilizing	0.552	D	0.74	deleterious	None	None	None	None	I
V/Q	0.3138	likely_benign	0.2994	benign	-0.586	Destabilizing	0.552	D	0.73	deleterious	None	None	None	None	I
V/R	0.2718	likely_benign	0.2444	benign	0.057	Stabilizing	0.378	N	0.728	deleterious	None	None	None	None	I
V/S	0.2613	likely_benign	0.2339	benign	-0.644	Destabilizing	0.233	N	0.584	neutral	None	None	None	None	I
V/T	0.143	likely_benign	0.1519	benign	-0.666	Destabilizing	0.001	N	0.311	neutral	None	None	None	None	I
V/W	0.8674	likely_pathogenic	0.8806	pathogenic	-1.112	Destabilizing	0.934	D	0.841	deleterious	None	None	None	None	I
V/Y	0.6186	likely_pathogenic	0.6075	pathogenic	-0.807	Destabilizing	0.552	D	0.589	neutral	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.