TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5119	15580;15581;15582	chr2:178734469;178734468;178734467	chr2:179599196;179599195;179599194
N2AB	4802	14629;14630;14631	chr2:178734469;178734468;178734467	chr2:179599196;179599195;179599194
N2A	3875	11848;11849;11850	chr2:178734469;178734468;178734467	chr2:179599196;179599195;179599194
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-34
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.9503
• 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/E	rs1183767493	None	0.248	N	0.243	0.205	0.322230723748	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	2.77362E-05	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	0.7525	likely_pathogenic	0.8435	pathogenic	-0.1	Destabilizing	0.97	D	0.473	neutral	None	None	None	None	N
K/C	0.9339	likely_pathogenic	0.9615	pathogenic	-0.655	Destabilizing	1.0	D	0.57	neutral	None	None	None	None	N
K/D	0.8804	likely_pathogenic	0.9283	pathogenic	-0.26	Destabilizing	0.942	D	0.477	neutral	None	None	None	None	N
K/E	0.6401	likely_pathogenic	0.7552	pathogenic	-0.274	Destabilizing	0.248	N	0.243	neutral	N	0.507973267	None	None	N
K/F	0.9695	likely_pathogenic	0.9854	pathogenic	-0.51	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
K/G	0.7159	likely_pathogenic	0.8107	pathogenic	-0.192	Destabilizing	0.985	D	0.462	neutral	None	None	None	None	N
K/H	0.6868	likely_pathogenic	0.7753	pathogenic	-0.257	Destabilizing	0.999	D	0.482	neutral	None	None	None	None	N
K/I	0.8549	likely_pathogenic	0.9193	pathogenic	0.06	Stabilizing	0.989	D	0.539	neutral	D	0.540289257	None	None	N
K/L	0.7722	likely_pathogenic	0.8524	pathogenic	0.06	Stabilizing	0.97	D	0.467	neutral	None	None	None	None	N
K/M	0.7527	likely_pathogenic	0.838	pathogenic	-0.284	Destabilizing	1.0	D	0.484	neutral	None	None	None	None	N
K/N	0.8245	likely_pathogenic	0.8931	pathogenic	-0.223	Destabilizing	0.98	D	0.448	neutral	N	0.514070265	None	None	N
K/P	0.755	likely_pathogenic	0.8395	pathogenic	0.027	Stabilizing	0.999	D	0.48	neutral	None	None	None	None	N
K/Q	0.3614	ambiguous	0.4707	ambiguous	-0.311	Destabilizing	0.689	D	0.255	neutral	N	0.502240912	None	None	N
K/R	0.0826	likely_benign	0.0947	benign	-0.244	Destabilizing	0.961	D	0.436	neutral	N	0.453410554	None	None	N
K/S	0.7675	likely_pathogenic	0.8518	pathogenic	-0.57	Destabilizing	0.942	D	0.439	neutral	None	None	None	None	N
K/T	0.6372	likely_pathogenic	0.7484	pathogenic	-0.477	Destabilizing	0.248	N	0.319	neutral	N	0.512486931	None	None	N
K/V	0.7697	likely_pathogenic	0.8586	pathogenic	0.027	Stabilizing	0.97	D	0.461	neutral	None	None	None	None	N
K/W	0.9328	likely_pathogenic	0.9614	pathogenic	-0.639	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	N
K/Y	0.9161	likely_pathogenic	0.9486	pathogenic	-0.294	Destabilizing	0.999	D	0.515	neutral	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.