TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29286	88081;88082;88083	chr2:178557406;178557405;178557404	chr2:179422133;179422132;179422131
N2AB	27645	83158;83159;83160	chr2:178557406;178557405;178557404	chr2:179422133;179422132;179422131
N2A	26718	80377;80378;80379	chr2:178557406;178557405;178557404	chr2:179422133;179422132;179422131
N2B	20221	60886;60887;60888	chr2:178557406;178557405;178557404	chr2:179422133;179422132;179422131
Novex-1	20346	61261;61262;61263	chr2:178557406;178557405;178557404	chr2:179422133;179422132;179422131
Novex-2	20413	61462;61463;61464	chr2:178557406;178557405;178557404	chr2:179422133;179422132;179422131
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: Fn3-101
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.2706
• Predicted PPI site: I

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/N	None	None	0.901	N	0.535	0.313	0.176091768786	gnomAD-4.0.0	3.18197E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71556E-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	0.7577	likely_pathogenic	0.7442	pathogenic	-0.256	Destabilizing	0.775	D	0.527	neutral	None	None	None	None	I
K/C	0.8957	likely_pathogenic	0.9128	pathogenic	-0.167	Destabilizing	0.996	D	0.743	deleterious	None	None	None	None	I
K/D	0.9424	likely_pathogenic	0.9416	pathogenic	-0.189	Destabilizing	0.923	D	0.649	neutral	None	None	None	None	I
K/E	0.6335	likely_pathogenic	0.6175	pathogenic	-0.117	Destabilizing	0.722	D	0.449	neutral	N	0.505565433	None	None	I
K/F	0.9548	likely_pathogenic	0.9515	pathogenic	-0.025	Destabilizing	0.987	D	0.753	deleterious	None	None	None	None	I
K/G	0.887	likely_pathogenic	0.8857	pathogenic	-0.595	Destabilizing	0.775	D	0.623	neutral	None	None	None	None	I
K/H	0.6028	likely_pathogenic	0.6142	pathogenic	-1.053	Destabilizing	0.989	D	0.719	prob.delet.	None	None	None	None	I
K/I	0.708	likely_pathogenic	0.6974	pathogenic	0.605	Stabilizing	0.901	D	0.758	deleterious	N	0.479446634	None	None	I
K/L	0.6597	likely_pathogenic	0.6582	pathogenic	0.605	Stabilizing	0.775	D	0.636	neutral	None	None	None	None	I
K/M	0.5229	ambiguous	0.5209	ambiguous	0.508	Stabilizing	0.996	D	0.716	prob.delet.	None	None	None	None	I
K/N	0.86	likely_pathogenic	0.848	pathogenic	-0.193	Destabilizing	0.901	D	0.535	neutral	N	0.485167399	None	None	I
K/P	0.7711	likely_pathogenic	0.7775	pathogenic	0.348	Stabilizing	0.987	D	0.706	prob.neutral	None	None	None	None	I
K/Q	0.33	likely_benign	0.3348	benign	-0.292	Destabilizing	0.901	D	0.552	neutral	N	0.476266629	None	None	I
K/R	0.0965	likely_benign	0.104	benign	-0.568	Destabilizing	0.008	N	0.197	neutral	N	0.489369403	None	None	I
K/S	0.8796	likely_pathogenic	0.8728	pathogenic	-0.704	Destabilizing	0.633	D	0.427	neutral	None	None	None	None	I
K/T	0.5294	ambiguous	0.5142	ambiguous	-0.448	Destabilizing	0.075	N	0.34	neutral	N	0.509147242	None	None	I
K/V	0.6327	likely_pathogenic	0.6321	pathogenic	0.348	Stabilizing	0.923	D	0.655	neutral	None	None	None	None	I
K/W	0.9346	likely_pathogenic	0.9452	pathogenic	0.026	Stabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	I
K/Y	0.8935	likely_pathogenic	0.8959	pathogenic	0.312	Stabilizing	0.987	D	0.755	deleterious	None	None	None	None	I

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.