TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9755	29488;29489;29490	chr2:178706611;178706610;178706609	chr2:179571338;179571337;179571336
N2AB	9438	28537;28538;28539	chr2:178706611;178706610;178706609	chr2:179571338;179571337;179571336
N2A	8511	25756;25757;25758	chr2:178706611;178706610;178706609	chr2:179571338;179571337;179571336
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-83
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.2954
• 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/Q	None	None	0.999	None	0.627	0.276	0.374255764437	gnomAD-4.0.0	1.59098E-06	None	None	None	None	N	None	5.65355E-05	0	None	0	0	None	0	0	0	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	0.7322	likely_pathogenic	0.6391	pathogenic	-0.904	Destabilizing	0.996	D	0.538	neutral	None	None	None	None	N
K/C	0.8477	likely_pathogenic	0.827	pathogenic	-0.983	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/D	0.9765	likely_pathogenic	0.9461	pathogenic	-1.334	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
K/E	0.5603	ambiguous	0.4282	ambiguous	-1.123	Destabilizing	0.998	D	0.483	neutral	None	None	None	None	N
K/F	0.8953	likely_pathogenic	0.8621	pathogenic	-0.142	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
K/G	0.9184	likely_pathogenic	0.8479	pathogenic	-1.368	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
K/H	0.5428	ambiguous	0.4967	ambiguous	-1.747	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/I	0.3945	ambiguous	0.3684	ambiguous	0.366	Stabilizing	0.994	D	0.728	prob.delet.	None	None	None	None	N
K/L	0.5558	ambiguous	0.4916	ambiguous	0.366	Stabilizing	0.269	N	0.514	neutral	None	None	None	None	N
K/M	0.3768	ambiguous	0.3232	benign	0.181	Stabilizing	0.998	D	0.772	deleterious	None	None	None	None	N
K/N	0.8782	likely_pathogenic	0.7969	pathogenic	-1.471	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	N
K/P	0.9975	likely_pathogenic	0.9924	pathogenic	-0.03	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/Q	0.2858	likely_benign	0.2347	benign	-1.253	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
K/R	0.1008	likely_benign	0.0972	benign	-1.346	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	N
K/S	0.8056	likely_pathogenic	0.7164	pathogenic	-1.924	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	N
K/T	0.3349	likely_benign	0.2775	benign	-1.486	Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	N
K/V	0.3728	ambiguous	0.345	ambiguous	-0.03	Destabilizing	0.983	D	0.651	neutral	None	None	None	None	N
K/W	0.9047	likely_pathogenic	0.8707	pathogenic	-0.234	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
K/Y	0.8249	likely_pathogenic	0.7773	pathogenic	0.087	Stabilizing	1.0	D	0.799	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.