TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4638	14137;14138;14139	chr2:178739321;178739320;178739319	chr2:179604048;179604047;179604046
N2AB	4321	13186;13187;13188	chr2:178739321;178739320;178739319	chr2:179604048;179604047;179604046
N2A	None	None	chr2:None	chr2:None
N2B	4275	13048;13049;13050	chr2:178739321;178739320;178739319	chr2:179604048;179604047;179604046
Novex-1	4400	13423;13424;13425	chr2:178739321;178739320;178739319	chr2:179604048;179604047;179604046
Novex-2	4467	13624;13625;13626	chr2:178739321;178739320;178739319	chr2:179604048;179604047;179604046
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-29
• Domain position: 33
• Structural Position: 49
• Q(SASA): 0.2142
• 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
Y/C	rs2082072923	None	0.994	D	0.601	0.397	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/N	rs376513367	None	0.979	D	0.614	0.43	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
Y/N	rs376513367	None	0.979	D	0.614	0.43	None	gnomAD-4.0.0	3.09865E-06	None	None	None	None	N	None	4.00406E-05	0	None	0	0	None	0	0	0	0	3.20256E-05

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
Y/A	0.6859	likely_pathogenic	0.7659	pathogenic	-2.748	Highly Destabilizing	0.742	D	0.559	neutral	None	None	None	None	N
Y/C	0.2365	likely_benign	0.2867	benign	-1.18	Destabilizing	0.994	D	0.601	neutral	D	0.6309323	None	None	N
Y/D	0.6497	likely_pathogenic	0.7249	pathogenic	-1.755	Destabilizing	0.979	D	0.627	neutral	D	0.592065061	None	None	N
Y/E	0.7924	likely_pathogenic	0.8416	pathogenic	-1.647	Destabilizing	0.984	D	0.611	neutral	None	None	None	None	N
Y/F	0.1054	likely_benign	0.1032	benign	-1.133	Destabilizing	0.003	N	0.179	neutral	N	0.44824334	None	None	N
Y/G	0.6304	likely_pathogenic	0.7069	pathogenic	-3.089	Highly Destabilizing	0.953	D	0.613	neutral	None	None	None	None	N
Y/H	0.1747	likely_benign	0.2068	benign	-1.437	Destabilizing	0.979	D	0.553	neutral	D	0.551042499	None	None	N
Y/I	0.4574	ambiguous	0.5595	ambiguous	-1.679	Destabilizing	0.59	D	0.516	neutral	None	None	None	None	N
Y/K	0.5873	likely_pathogenic	0.6705	pathogenic	-1.434	Destabilizing	0.953	D	0.611	neutral	None	None	None	None	N
Y/L	0.402	ambiguous	0.5237	ambiguous	-1.679	Destabilizing	0.004	N	0.292	neutral	None	None	None	None	N
Y/M	0.6463	likely_pathogenic	0.7092	pathogenic	-1.258	Destabilizing	0.91	D	0.58	neutral	None	None	None	None	N
Y/N	0.2669	likely_benign	0.3342	benign	-1.75	Destabilizing	0.979	D	0.614	neutral	D	0.592065061	None	None	N
Y/P	0.9823	likely_pathogenic	0.99	pathogenic	-2.036	Highly Destabilizing	0.984	D	0.633	neutral	None	None	None	None	N
Y/Q	0.5882	likely_pathogenic	0.6823	pathogenic	-1.714	Destabilizing	0.984	D	0.584	neutral	None	None	None	None	N
Y/R	0.4091	ambiguous	0.5043	ambiguous	-0.926	Destabilizing	0.984	D	0.616	neutral	None	None	None	None	N
Y/S	0.3733	ambiguous	0.4593	ambiguous	-2.278	Highly Destabilizing	0.815	D	0.609	neutral	N	0.506627612	None	None	N
Y/T	0.612	likely_pathogenic	0.6943	pathogenic	-2.077	Highly Destabilizing	0.854	D	0.594	neutral	None	None	None	None	N
Y/V	0.4628	ambiguous	0.5555	ambiguous	-2.036	Highly Destabilizing	0.373	N	0.511	neutral	None	None	None	None	N
Y/W	0.4404	ambiguous	0.4646	ambiguous	-0.594	Destabilizing	0.984	D	0.551	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.