TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19102	57529;57530;57531	chr2:178597778;178597777;178597776	chr2:179462505;179462504;179462503
N2AB	17461	52606;52607;52608	chr2:178597778;178597777;178597776	chr2:179462505;179462504;179462503
N2A	16534	49825;49826;49827	chr2:178597778;178597777;178597776	chr2:179462505;179462504;179462503
N2B	10037	30334;30335;30336	chr2:178597778;178597777;178597776	chr2:179462505;179462504;179462503
Novex-1	10162	30709;30710;30711	chr2:178597778;178597777;178597776	chr2:179462505;179462504;179462503
Novex-2	10229	30910;30911;30912	chr2:178597778;178597777;178597776	chr2:179462505;179462504;179462503
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: Ig-117
• Domain position: 8
• Structural Position: 13
• Q(SASA): 0.2194
• 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
I/T	rs878854319	-2.151	1.0	N	0.691	0.547	0.785196952754	gnomAD-4.0.0	1.59256E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43316E-05	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	0.8507	likely_pathogenic	0.8754	pathogenic	-2.238	Highly Destabilizing	0.999	D	0.483	neutral	None	None	None	None	I
I/C	0.9299	likely_pathogenic	0.942	pathogenic	-1.531	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
I/D	0.9916	likely_pathogenic	0.9938	pathogenic	-2.188	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
I/E	0.9636	likely_pathogenic	0.9688	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
I/F	0.3951	ambiguous	0.4918	ambiguous	-1.308	Destabilizing	1.0	D	0.704	prob.neutral	N	0.516295887	None	None	I
I/G	0.9818	likely_pathogenic	0.9856	pathogenic	-2.727	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
I/H	0.9158	likely_pathogenic	0.9424	pathogenic	-2.052	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
I/K	0.8979	likely_pathogenic	0.9262	pathogenic	-1.894	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
I/L	0.1507	likely_benign	0.1771	benign	-0.869	Destabilizing	0.993	D	0.382	neutral	N	0.467410555	None	None	I
I/M	0.1244	likely_benign	0.1495	benign	-0.72	Destabilizing	1.0	D	0.717	prob.delet.	N	0.486999181	None	None	I
I/N	0.9163	likely_pathogenic	0.9377	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.831	deleterious	N	0.517056355	None	None	I
I/P	0.9913	likely_pathogenic	0.9944	pathogenic	-1.301	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
I/Q	0.8942	likely_pathogenic	0.9065	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
I/R	0.8643	likely_pathogenic	0.9091	pathogenic	-1.469	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
I/S	0.9136	likely_pathogenic	0.9313	pathogenic	-2.75	Highly Destabilizing	1.0	D	0.771	deleterious	N	0.504686092	None	None	I
I/T	0.7963	likely_pathogenic	0.8255	pathogenic	-2.447	Highly Destabilizing	1.0	D	0.691	prob.neutral	N	0.489037372	None	None	I
I/V	0.1571	likely_benign	0.161	benign	-1.301	Destabilizing	0.993	D	0.364	neutral	N	0.470754718	None	None	I
I/W	0.9285	likely_pathogenic	0.9598	pathogenic	-1.62	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
I/Y	0.8228	likely_pathogenic	0.877	pathogenic	-1.338	Destabilizing	1.0	D	0.775	deleterious	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.