TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14525	43798;43799;43800	chr2:178632321;178632320;178632319	chr2:179497048;179497047;179497046
N2AB	12884	38875;38876;38877	chr2:178632321;178632320;178632319	chr2:179497048;179497047;179497046
N2A	11957	36094;36095;36096	chr2:178632321;178632320;178632319	chr2:179497048;179497047;179497046
N2B	5460	16603;16604;16605	chr2:178632321;178632320;178632319	chr2:179497048;179497047;179497046
Novex-1	5585	16978;16979;16980	chr2:178632321;178632320;178632319	chr2:179497048;179497047;179497046
Novex-2	5652	17179;17180;17181	chr2:178632321;178632320;178632319	chr2:179497048;179497047;179497046
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-96
• Domain position: 29
• Structural Position: 44
• Q(SASA): 0.2245
• 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	rs2059904805	None	0.198	N	0.217	0.091	0.306377322295	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
I/V	rs2059904805	None	0.198	N	0.217	0.091	0.306377322295	gnomAD-4.0.0	6.57549E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07039E-04	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	0.8781	likely_pathogenic	0.8258	pathogenic	-1.989	Destabilizing	0.983	D	0.451	neutral	None	None	None	None	N
I/C	0.9345	likely_pathogenic	0.9115	pathogenic	-0.915	Destabilizing	1.0	D	0.584	neutral	None	None	None	None	N
I/D	0.9737	likely_pathogenic	0.9592	pathogenic	-1.731	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
I/E	0.9353	likely_pathogenic	0.9082	pathogenic	-1.694	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
I/F	0.4669	ambiguous	0.3811	ambiguous	-1.425	Destabilizing	0.997	D	0.565	neutral	D	0.553065249	None	None	N
I/G	0.9686	likely_pathogenic	0.954	pathogenic	-2.337	Highly Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
I/H	0.9022	likely_pathogenic	0.8685	pathogenic	-1.644	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
I/K	0.882	likely_pathogenic	0.8459	pathogenic	-1.409	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
I/L	0.3179	likely_benign	0.2613	benign	-1.064	Destabilizing	0.798	D	0.437	neutral	N	0.503149385	None	None	N
I/M	0.3272	likely_benign	0.2826	benign	-0.738	Destabilizing	0.997	D	0.541	neutral	N	0.485202952	None	None	N
I/N	0.7911	likely_pathogenic	0.7316	pathogenic	-1.12	Destabilizing	0.999	D	0.708	prob.delet.	D	0.55499867	None	None	N
I/P	0.9495	likely_pathogenic	0.9332	pathogenic	-1.346	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
I/Q	0.894	likely_pathogenic	0.8596	pathogenic	-1.268	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
I/R	0.8189	likely_pathogenic	0.7677	pathogenic	-0.864	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
I/S	0.8197	likely_pathogenic	0.7672	pathogenic	-1.644	Destabilizing	0.997	D	0.604	neutral	N	0.511041152	None	None	N
I/T	0.7871	likely_pathogenic	0.7246	pathogenic	-1.494	Destabilizing	0.978	D	0.574	neutral	N	0.511041152	None	None	N
I/V	0.1625	likely_benign	0.1395	benign	-1.346	Destabilizing	0.198	N	0.217	neutral	N	0.421867914	None	None	N
I/W	0.9584	likely_pathogenic	0.9472	pathogenic	-1.541	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
I/Y	0.8443	likely_pathogenic	0.7935	pathogenic	-1.353	Destabilizing	0.999	D	0.596	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.