TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28559	85900;85901;85902	chr2:178560457;178560456;178560455	chr2:179425184;179425183;179425182
N2AB	26918	80977;80978;80979	chr2:178560457;178560456;178560455	chr2:179425184;179425183;179425182
N2A	25991	78196;78197;78198	chr2:178560457;178560456;178560455	chr2:179425184;179425183;179425182
N2B	19494	58705;58706;58707	chr2:178560457;178560456;178560455	chr2:179425184;179425183;179425182
Novex-1	19619	59080;59081;59082	chr2:178560457;178560456;178560455	chr2:179425184;179425183;179425182
Novex-2	19686	59281;59282;59283	chr2:178560457;178560456;178560455	chr2:179425184;179425183;179425182
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-96
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2512
• 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
I/V	rs1156788911	-1.212	None	N	0.168	0.078	0.20549828249	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/V	rs1156788911	-1.212	None	N	0.168	0.078	0.20549828249	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85863E-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
I/A	0.669	likely_pathogenic	0.6136	pathogenic	-2.493	Highly Destabilizing	0.116	N	0.509	neutral	None	None	None	None	N
I/C	0.7779	likely_pathogenic	0.7621	pathogenic	-1.745	Destabilizing	0.944	D	0.611	neutral	None	None	None	None	N
I/D	0.9596	likely_pathogenic	0.945	pathogenic	-2.451	Highly Destabilizing	0.818	D	0.707	prob.neutral	None	None	None	None	N
I/E	0.9205	likely_pathogenic	0.8958	pathogenic	-2.254	Highly Destabilizing	0.818	D	0.706	prob.neutral	None	None	None	None	N
I/F	0.3789	ambiguous	0.3044	benign	-1.514	Destabilizing	0.627	D	0.589	neutral	N	0.491254915	None	None	N
I/G	0.9187	likely_pathogenic	0.8928	pathogenic	-3.031	Highly Destabilizing	0.818	D	0.709	prob.delet.	None	None	None	None	N
I/H	0.9176	likely_pathogenic	0.8845	pathogenic	-2.404	Highly Destabilizing	0.981	D	0.693	prob.neutral	None	None	None	None	N
I/K	0.8472	likely_pathogenic	0.8212	pathogenic	-1.9	Destabilizing	0.818	D	0.709	prob.delet.	None	None	None	None	N
I/L	0.22	likely_benign	0.1857	benign	-0.96	Destabilizing	0.001	N	0.213	neutral	N	0.474266665	None	None	N
I/M	0.1718	likely_benign	0.1547	benign	-0.82	Destabilizing	0.627	D	0.57	neutral	N	0.471675181	None	None	N
I/N	0.6884	likely_pathogenic	0.6313	pathogenic	-2.102	Highly Destabilizing	0.912	D	0.713	prob.delet.	N	0.500414952	None	None	N
I/P	0.8127	likely_pathogenic	0.7931	pathogenic	-1.449	Destabilizing	0.932	D	0.706	prob.neutral	None	None	None	None	N
I/Q	0.8929	likely_pathogenic	0.8583	pathogenic	-2.007	Highly Destabilizing	0.932	D	0.709	prob.delet.	None	None	None	None	N
I/R	0.8287	likely_pathogenic	0.79	pathogenic	-1.572	Destabilizing	0.818	D	0.713	prob.delet.	None	None	None	None	N
I/S	0.771	likely_pathogenic	0.7004	pathogenic	-2.849	Highly Destabilizing	0.627	D	0.649	neutral	N	0.476941873	None	None	N
I/T	0.6771	likely_pathogenic	0.6163	pathogenic	-2.498	Highly Destabilizing	0.324	N	0.598	neutral	N	0.473409927	None	None	N
I/V	0.0882	likely_benign	0.079	benign	-1.449	Destabilizing	None	N	0.168	neutral	N	0.372656876	None	None	N
I/W	0.9417	likely_pathogenic	0.9246	pathogenic	-1.834	Destabilizing	0.981	D	0.718	prob.delet.	None	None	None	None	N
I/Y	0.7853	likely_pathogenic	0.727	pathogenic	-1.565	Destabilizing	0.818	D	0.627	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.