TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33269	100030;100031;100032	chr2:178537402;178537401;178537400	chr2:179402129;179402128;179402127
N2AB	31628	95107;95108;95109	chr2:178537402;178537401;178537400	chr2:179402129;179402128;179402127
N2A	30701	92326;92327;92328	chr2:178537402;178537401;178537400	chr2:179402129;179402128;179402127
N2B	24204	72835;72836;72837	chr2:178537402;178537401;178537400	chr2:179402129;179402128;179402127
Novex-1	24329	73210;73211;73212	chr2:178537402;178537401;178537400	chr2:179402129;179402128;179402127
Novex-2	24396	73411;73412;73413	chr2:178537402;178537401;178537400	chr2:179402129;179402128;179402127
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-157
• Domain position: 67
• Structural Position: 155
• Q(SASA): 0.1601
• 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/R	None	None	0.192	N	0.375	0.095	0.101711395817	gnomAD-4.0.0	1.60617E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89256E-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	0.7267	likely_pathogenic	0.6227	pathogenic	-1.35	Destabilizing	0.996	D	0.563	neutral	None	None	None	None	N
K/C	0.8554	likely_pathogenic	0.8195	pathogenic	-1.59	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/D	0.9471	likely_pathogenic	0.9044	pathogenic	-1.21	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
K/E	0.5115	ambiguous	0.3777	ambiguous	-0.99	Destabilizing	0.981	D	0.459	neutral	N	0.440777662	None	None	N
K/F	0.9351	likely_pathogenic	0.9106	pathogenic	-0.82	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
K/G	0.8826	likely_pathogenic	0.8206	pathogenic	-1.768	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
K/H	0.4658	ambiguous	0.3763	ambiguous	-1.884	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/I	0.6147	likely_pathogenic	0.5158	ambiguous	-0.205	Destabilizing	0.974	D	0.81	deleterious	N	0.459190064	None	None	N
K/L	0.6674	likely_pathogenic	0.585	pathogenic	-0.205	Destabilizing	0.96	D	0.709	prob.delet.	None	None	None	None	N
K/M	0.4425	ambiguous	0.3528	ambiguous	-0.513	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
K/N	0.7992	likely_pathogenic	0.6963	pathogenic	-1.365	Destabilizing	0.998	D	0.689	prob.neutral	N	0.468041621	None	None	N
K/P	0.9965	likely_pathogenic	0.994	pathogenic	-0.563	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
K/Q	0.2526	likely_benign	0.1917	benign	-1.266	Destabilizing	0.987	D	0.684	prob.neutral	N	0.477949183	None	None	N
K/R	0.0986	likely_benign	0.0916	benign	-0.959	Destabilizing	0.192	N	0.375	neutral	N	0.418092803	None	None	N
K/S	0.7656	likely_pathogenic	0.6665	pathogenic	-2.038	Highly Destabilizing	0.996	D	0.569	neutral	None	None	None	None	N
K/T	0.3516	ambiguous	0.2604	benign	-1.583	Destabilizing	0.995	D	0.732	prob.delet.	N	0.367565195	None	None	N
K/V	0.5912	likely_pathogenic	0.5083	ambiguous	-0.563	Destabilizing	0.97	D	0.777	deleterious	None	None	None	None	N
K/W	0.9318	likely_pathogenic	0.9004	pathogenic	-0.728	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/Y	0.8661	likely_pathogenic	0.8125	pathogenic	-0.385	Destabilizing	0.996	D	0.821	deleterious	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.