TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33133	99622;99623;99624	chr2:178537810;178537809;178537808	chr2:179402537;179402536;179402535
N2AB	31492	94699;94700;94701	chr2:178537810;178537809;178537808	chr2:179402537;179402536;179402535
N2A	30565	91918;91919;91920	chr2:178537810;178537809;178537808	chr2:179402537;179402536;179402535
N2B	24068	72427;72428;72429	chr2:178537810;178537809;178537808	chr2:179402537;179402536;179402535
Novex-1	24193	72802;72803;72804	chr2:178537810;178537809;178537808	chr2:179402537;179402536;179402535
Novex-2	24260	73003;73004;73005	chr2:178537810;178537809;178537808	chr2:179402537;179402536;179402535
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-156
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.3977
• 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
K/T	rs794729552	None	0.998	N	0.665	0.527	0.36893422563	gnomAD-4.0.0	1.59145E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85851E-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
K/A	0.6525	likely_pathogenic	0.7235	pathogenic	-0.852	Destabilizing	0.995	D	0.571	neutral	None	None	None	None	N
K/C	0.7669	likely_pathogenic	0.8411	pathogenic	-0.782	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/D	0.921	likely_pathogenic	0.9376	pathogenic	-0.642	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/E	0.4647	ambiguous	0.5051	ambiguous	-0.449	Destabilizing	0.959	D	0.509	neutral	N	0.456750844	None	None	N
K/F	0.9252	likely_pathogenic	0.9489	pathogenic	-0.184	Destabilizing	0.997	D	0.756	deleterious	None	None	None	None	N
K/G	0.8096	likely_pathogenic	0.8578	pathogenic	-1.293	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
K/H	0.3803	ambiguous	0.476	ambiguous	-1.476	Destabilizing	0.239	N	0.499	neutral	None	None	None	None	N
K/I	0.6007	likely_pathogenic	0.646	pathogenic	0.339	Stabilizing	0.98	D	0.748	deleterious	N	0.493367792	None	None	N
K/L	0.6265	likely_pathogenic	0.6858	pathogenic	0.339	Stabilizing	0.956	D	0.666	neutral	None	None	None	None	N
K/M	0.4722	ambiguous	0.5276	ambiguous	0.082	Stabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/N	0.7303	likely_pathogenic	0.778	pathogenic	-1.016	Destabilizing	0.996	D	0.645	neutral	D	0.535771775	None	None	N
K/P	0.995	likely_pathogenic	0.995	pathogenic	-0.03	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/Q	0.1797	likely_benign	0.2169	benign	-0.881	Destabilizing	0.985	D	0.653	neutral	N	0.477435548	None	None	N
K/R	0.0956	likely_benign	0.1057	benign	-0.88	Destabilizing	0.967	D	0.52	neutral	N	0.451654456	None	None	N
K/S	0.6399	likely_pathogenic	0.7162	pathogenic	-1.597	Destabilizing	0.995	D	0.577	neutral	None	None	None	None	N
K/T	0.3007	likely_benign	0.355	ambiguous	-1.174	Destabilizing	0.998	D	0.665	neutral	N	0.382562517	None	None	N
K/V	0.5533	ambiguous	0.6128	pathogenic	-0.03	Destabilizing	0.989	D	0.694	prob.neutral	None	None	None	None	N
K/W	0.9247	likely_pathogenic	0.9506	pathogenic	-0.138	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/Y	0.861	likely_pathogenic	0.8972	pathogenic	0.135	Stabilizing	0.945	D	0.715	prob.delet.	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.