TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22853	68782;68783;68784	chr2:178577869;178577868;178577867	chr2:179442596;179442595;179442594
N2AB	21212	63859;63860;63861	chr2:178577869;178577868;178577867	chr2:179442596;179442595;179442594
N2A	20285	61078;61079;61080	chr2:178577869;178577868;178577867	chr2:179442596;179442595;179442594
N2B	13788	41587;41588;41589	chr2:178577869;178577868;178577867	chr2:179442596;179442595;179442594
Novex-1	13913	41962;41963;41964	chr2:178577869;178577868;178577867	chr2:179442596;179442595;179442594
Novex-2	13980	42163;42164;42165	chr2:178577869;178577868;178577867	chr2:179442596;179442595;179442594
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-54
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2228
• 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/L	None	None	None	N	0.051	0.147	0.435152311215	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

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	0.4637	ambiguous	0.4327	ambiguous	-1.765	Destabilizing	0.007	N	0.229	neutral	None	None	None	None	N
I/C	0.6734	likely_pathogenic	0.6488	pathogenic	-1.808	Destabilizing	0.356	N	0.363	neutral	None	None	None	None	N
I/D	0.8899	likely_pathogenic	0.8795	pathogenic	-2.285	Highly Destabilizing	0.356	N	0.517	neutral	None	None	None	None	N
I/E	0.7527	likely_pathogenic	0.7613	pathogenic	-2.271	Highly Destabilizing	0.136	N	0.458	neutral	None	None	None	None	N
I/F	0.3845	ambiguous	0.3513	ambiguous	-1.535	Destabilizing	0.072	N	0.276	neutral	None	None	None	None	N
I/G	0.7912	likely_pathogenic	0.7421	pathogenic	-2.07	Highly Destabilizing	0.136	N	0.436	neutral	None	None	None	None	N
I/H	0.73	likely_pathogenic	0.7173	pathogenic	-1.379	Destabilizing	0.864	D	0.409	neutral	None	None	None	None	N
I/K	0.4787	ambiguous	0.5225	ambiguous	-1.307	Destabilizing	0.106	N	0.444	neutral	N	0.509998178	None	None	N
I/L	0.2376	likely_benign	0.2155	benign	-0.983	Destabilizing	None	N	0.051	neutral	N	0.519367023	None	None	N
I/M	0.1621	likely_benign	0.1562	benign	-1.021	Destabilizing	0.171	N	0.377	neutral	N	0.493439967	None	None	N
I/N	0.4728	ambiguous	0.4745	ambiguous	-1.359	Destabilizing	0.628	D	0.491	neutral	None	None	None	None	N
I/P	0.9355	likely_pathogenic	0.9206	pathogenic	-1.216	Destabilizing	0.356	N	0.516	neutral	None	None	None	None	N
I/Q	0.6076	likely_pathogenic	0.615	pathogenic	-1.61	Destabilizing	0.628	D	0.487	neutral	None	None	None	None	N
I/R	0.4179	ambiguous	0.4379	ambiguous	-0.745	Destabilizing	0.295	N	0.497	neutral	N	0.476625931	None	None	N
I/S	0.4102	ambiguous	0.3955	ambiguous	-1.886	Destabilizing	0.072	N	0.397	neutral	None	None	None	None	N
I/T	0.2282	likely_benign	0.2405	benign	-1.756	Destabilizing	0.012	N	0.363	neutral	N	0.469206419	None	None	N
I/V	0.0589	likely_benign	0.0568	benign	-1.216	Destabilizing	None	N	0.065	neutral	N	0.399595548	None	None	N
I/W	0.933	likely_pathogenic	0.9157	pathogenic	-1.638	Destabilizing	0.864	D	0.417	neutral	None	None	None	None	N
I/Y	0.7085	likely_pathogenic	0.6788	pathogenic	-1.331	Destabilizing	0.136	N	0.462	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.