TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31965	96118;96119;96120	chr2:178544336;178544335;178544334	chr2:179409063;179409062;179409061
N2AB	30324	91195;91196;91197	chr2:178544336;178544335;178544334	chr2:179409063;179409062;179409061
N2A	29397	88414;88415;88416	chr2:178544336;178544335;178544334	chr2:179409063;179409062;179409061
N2B	22900	68923;68924;68925	chr2:178544336;178544335;178544334	chr2:179409063;179409062;179409061
Novex-1	23025	69298;69299;69300	chr2:178544336;178544335;178544334	chr2:179409063;179409062;179409061
Novex-2	23092	69499;69500;69501	chr2:178544336;178544335;178544334	chr2:179409063;179409062;179409061
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: Fn3-121
• Domain position: 57
• Structural Position: 77
• Q(SASA): 0.0554
• 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	rs1696027685	None	0.041	N	0.401	0.028	0.233785782151	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.7199	likely_pathogenic	0.7131	pathogenic	-2.519	Highly Destabilizing	0.207	N	0.577	neutral	None	None	None	None	N
I/C	0.8026	likely_pathogenic	0.8152	pathogenic	-1.801	Destabilizing	0.981	D	0.631	neutral	None	None	None	None	N
I/D	0.9644	likely_pathogenic	0.962	pathogenic	-3.086	Highly Destabilizing	0.932	D	0.682	prob.neutral	None	None	None	None	N
I/E	0.9128	likely_pathogenic	0.9044	pathogenic	-2.803	Highly Destabilizing	0.818	D	0.671	neutral	None	None	None	None	N
I/F	0.3449	ambiguous	0.3617	ambiguous	-1.452	Destabilizing	0.527	D	0.627	neutral	None	None	None	None	N
I/G	0.9233	likely_pathogenic	0.9201	pathogenic	-3.119	Highly Destabilizing	0.818	D	0.652	neutral	None	None	None	None	N
I/H	0.8747	likely_pathogenic	0.8688	pathogenic	-2.764	Highly Destabilizing	0.981	D	0.689	prob.neutral	None	None	None	None	N
I/K	0.8404	likely_pathogenic	0.8277	pathogenic	-1.818	Destabilizing	0.773	D	0.651	neutral	N	0.517654869	None	None	N
I/L	0.1033	likely_benign	0.0992	benign	-0.748	Destabilizing	None	N	0.198	neutral	N	0.411081978	None	None	N
I/M	0.1673	likely_benign	0.1703	benign	-0.822	Destabilizing	0.627	D	0.653	neutral	N	0.518001586	None	None	N
I/N	0.7503	likely_pathogenic	0.7388	pathogenic	-2.339	Highly Destabilizing	0.932	D	0.699	prob.neutral	None	None	None	None	N
I/P	0.9443	likely_pathogenic	0.9399	pathogenic	-1.324	Destabilizing	0.932	D	0.699	prob.neutral	None	None	None	None	N
I/Q	0.8307	likely_pathogenic	0.8201	pathogenic	-2.086	Highly Destabilizing	0.932	D	0.695	prob.neutral	None	None	None	None	N
I/R	0.7933	likely_pathogenic	0.7734	pathogenic	-1.756	Destabilizing	0.773	D	0.688	prob.neutral	N	0.513190412	None	None	N
I/S	0.7745	likely_pathogenic	0.761	pathogenic	-2.999	Highly Destabilizing	0.818	D	0.641	neutral	None	None	None	None	N
I/T	0.7489	likely_pathogenic	0.7337	pathogenic	-2.556	Highly Destabilizing	0.324	N	0.614	neutral	N	0.451872595	None	None	N
I/V	0.0933	likely_benign	0.0939	benign	-1.324	Destabilizing	0.041	N	0.401	neutral	N	0.4328199	None	None	N
I/W	0.8992	likely_pathogenic	0.9044	pathogenic	-1.932	Destabilizing	0.981	D	0.707	prob.neutral	None	None	None	None	N
I/Y	0.7723	likely_pathogenic	0.7823	pathogenic	-1.63	Destabilizing	0.818	D	0.655	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.