TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24214	72865;72866;72867	chr2:178573492;178573491;178573490	chr2:179438219;179438218;179438217
N2AB	22573	67942;67943;67944	chr2:178573492;178573491;178573490	chr2:179438219;179438218;179438217
N2A	21646	65161;65162;65163	chr2:178573492;178573491;178573490	chr2:179438219;179438218;179438217
N2B	15149	45670;45671;45672	chr2:178573492;178573491;178573490	chr2:179438219;179438218;179438217
Novex-1	15274	46045;46046;46047	chr2:178573492;178573491;178573490	chr2:179438219;179438218;179438217
Novex-2	15341	46246;46247;46248	chr2:178573492;178573491;178573490	chr2:179438219;179438218;179438217
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-63
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.2695
• 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
V/L	None	None	0.002	N	0.331	0.125	0.322786055943	gnomAD-4.0.0	7.406E-07	None	None	None	None	N	None	3.34986E-05	0	None	0	0	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	0.2136	likely_benign	0.2686	benign	-1.492	Destabilizing	0.001	N	0.174	neutral	N	0.483268068	None	None	N
V/C	0.563	ambiguous	0.6418	pathogenic	-0.977	Destabilizing	0.869	D	0.539	neutral	None	None	None	None	N
V/D	0.6802	likely_pathogenic	0.7469	pathogenic	-1.433	Destabilizing	0.221	N	0.696	prob.delet.	None	None	None	None	N
V/E	0.468	ambiguous	0.5202	ambiguous	-1.346	Destabilizing	0.058	N	0.563	neutral	N	0.468570854	None	None	N
V/F	0.1669	likely_benign	0.2187	benign	-0.912	Destabilizing	0.221	N	0.587	neutral	None	None	None	None	N
V/G	0.3309	likely_benign	0.4169	ambiguous	-1.891	Destabilizing	0.03	N	0.634	neutral	N	0.514503055	None	None	N
V/H	0.6159	likely_pathogenic	0.7012	pathogenic	-1.387	Destabilizing	0.869	D	0.705	prob.delet.	None	None	None	None	N
V/I	0.0726	likely_benign	0.0752	benign	-0.461	Destabilizing	None	N	0.145	neutral	None	None	None	None	N
V/K	0.4038	ambiguous	0.4989	ambiguous	-1.351	Destabilizing	0.075	N	0.537	neutral	None	None	None	None	N
V/L	0.1331	likely_benign	0.1845	benign	-0.461	Destabilizing	0.002	N	0.331	neutral	N	0.469630357	None	None	N
V/M	0.1123	likely_benign	0.1485	benign	-0.393	Destabilizing	0.002	N	0.333	neutral	N	0.468913249	None	None	N
V/N	0.4804	ambiguous	0.5812	pathogenic	-1.324	Destabilizing	0.221	N	0.711	prob.delet.	None	None	None	None	N
V/P	0.934	likely_pathogenic	0.9519	pathogenic	-0.772	Destabilizing	0.366	N	0.581	neutral	None	None	None	None	N
V/Q	0.3643	ambiguous	0.4514	ambiguous	-1.351	Destabilizing	0.221	N	0.601	neutral	None	None	None	None	N
V/R	0.3655	ambiguous	0.4642	ambiguous	-0.947	Destabilizing	0.221	N	0.708	prob.delet.	None	None	None	None	N
V/S	0.3069	likely_benign	0.3843	ambiguous	-1.886	Destabilizing	0.039	N	0.539	neutral	None	None	None	None	N
V/T	0.1885	likely_benign	0.2297	benign	-1.672	Destabilizing	None	N	0.171	neutral	None	None	None	None	N
V/W	0.8109	likely_pathogenic	0.8751	pathogenic	-1.223	Destabilizing	0.869	D	0.739	deleterious	None	None	None	None	N
V/Y	0.5343	ambiguous	0.6438	pathogenic	-0.876	Destabilizing	0.366	N	0.573	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.