TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32243	96952;96953;96954	chr2:178543246;178543245;178543244	chr2:179407973;179407972;179407971
N2AB	30602	92029;92030;92031	chr2:178543246;178543245;178543244	chr2:179407973;179407972;179407971
N2A	29675	89248;89249;89250	chr2:178543246;178543245;178543244	chr2:179407973;179407972;179407971
N2B	23178	69757;69758;69759	chr2:178543246;178543245;178543244	chr2:179407973;179407972;179407971
Novex-1	23303	70132;70133;70134	chr2:178543246;178543245;178543244	chr2:179407973;179407972;179407971
Novex-2	23370	70333;70334;70335	chr2:178543246;178543245;178543244	chr2:179407973;179407972;179407971
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: Fn3-123
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3649
• 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/N	None	None	0.638	N	0.601	0.109	0.19670166235	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
K/A	0.5467	ambiguous	0.5131	ambiguous	-0.43	Destabilizing	0.399	N	0.514	neutral	None	None	None	None	N
K/C	0.8072	likely_pathogenic	0.787	pathogenic	-0.388	Destabilizing	0.982	D	0.725	prob.delet.	None	None	None	None	N
K/D	0.8945	likely_pathogenic	0.8778	pathogenic	0.086	Stabilizing	0.7	D	0.709	prob.delet.	None	None	None	None	N
K/E	0.4022	ambiguous	0.3681	ambiguous	0.159	Stabilizing	0.201	N	0.442	neutral	N	0.462548161	None	None	N
K/F	0.9022	likely_pathogenic	0.8707	pathogenic	-0.336	Destabilizing	0.947	D	0.736	prob.delet.	None	None	None	None	N
K/G	0.6999	likely_pathogenic	0.6611	pathogenic	-0.74	Destabilizing	0.7	D	0.588	neutral	None	None	None	None	N
K/H	0.5037	ambiguous	0.4853	ambiguous	-1.109	Destabilizing	0.947	D	0.693	prob.neutral	None	None	None	None	N
K/I	0.5546	ambiguous	0.5002	ambiguous	0.344	Stabilizing	0.781	D	0.771	deleterious	N	0.519983099	None	None	N
K/L	0.4732	ambiguous	0.4333	ambiguous	0.344	Stabilizing	0.7	D	0.588	neutral	None	None	None	None	N
K/M	0.4213	ambiguous	0.3907	ambiguous	0.217	Stabilizing	0.982	D	0.683	prob.neutral	None	None	None	None	N
K/N	0.7952	likely_pathogenic	0.7733	pathogenic	-0.157	Destabilizing	0.638	D	0.601	neutral	N	0.491294987	None	None	N
K/P	0.615	likely_pathogenic	0.6199	pathogenic	0.117	Stabilizing	0.826	D	0.735	prob.delet.	None	None	None	None	N
K/Q	0.2167	likely_benign	0.2125	benign	-0.254	Destabilizing	0.468	N	0.597	neutral	N	0.482270072	None	None	N
K/R	0.0774	likely_benign	0.0767	benign	-0.417	Destabilizing	0.002	N	0.175	neutral	N	0.471074431	None	None	N
K/S	0.7328	likely_pathogenic	0.7002	pathogenic	-0.778	Destabilizing	0.399	N	0.536	neutral	None	None	None	None	N
K/T	0.4323	ambiguous	0.409	ambiguous	-0.51	Destabilizing	0.638	D	0.637	neutral	N	0.49579673	None	None	N
K/V	0.4838	ambiguous	0.4359	ambiguous	0.117	Stabilizing	0.7	D	0.714	prob.delet.	None	None	None	None	N
K/W	0.8624	likely_pathogenic	0.837	pathogenic	-0.247	Destabilizing	0.982	D	0.711	prob.delet.	None	None	None	None	N
K/Y	0.8284	likely_pathogenic	0.7922	pathogenic	0.055	Stabilizing	0.826	D	0.722	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.