TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13806	41641;41642;41643	chr2:178636155;178636154;178636153	chr2:179500882;179500881;179500880
N2AB	12165	36718;36719;36720	chr2:178636155;178636154;178636153	chr2:179500882;179500881;179500880
N2A	11238	33937;33938;33939	chr2:178636155;178636154;178636153	chr2:179500882;179500881;179500880
N2B	4741	14446;14447;14448	chr2:178636155;178636154;178636153	chr2:179500882;179500881;179500880
Novex-1	4866	14821;14822;14823	chr2:178636155;178636154;178636153	chr2:179500882;179500881;179500880
Novex-2	4933	15022;15023;15024	chr2:178636155;178636154;178636153	chr2:179500882;179500881;179500880
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-88
• Domain position: 27
• Structural Position: 40
• Q(SASA): 0.7509
• 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	rs767727056	0.027	1.0	N	0.803	0.18	0.117506650769	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/N	rs767727056	0.027	1.0	N	0.803	0.18	0.117506650769	gnomAD-4.0.0	1.59306E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86079E-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	0.8838	likely_pathogenic	0.8602	pathogenic	0.008	Stabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
K/C	0.9635	likely_pathogenic	0.9541	pathogenic	-0.396	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
K/D	0.9771	likely_pathogenic	0.9713	pathogenic	-0.018	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/E	0.6677	likely_pathogenic	0.6468	pathogenic	0.035	Stabilizing	0.999	D	0.697	prob.delet.	N	0.319113964	None	None	N
K/F	0.9871	likely_pathogenic	0.9836	pathogenic	-0.011	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
K/G	0.921	likely_pathogenic	0.9051	pathogenic	-0.238	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/H	0.8317	likely_pathogenic	0.786	pathogenic	-0.378	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
K/I	0.8777	likely_pathogenic	0.868	pathogenic	0.593	Stabilizing	1.0	D	0.754	deleterious	N	0.357388891	None	None	N
K/L	0.8582	likely_pathogenic	0.8373	pathogenic	0.593	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/M	0.7607	likely_pathogenic	0.7281	pathogenic	0.081	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/N	0.9515	likely_pathogenic	0.9404	pathogenic	-0.072	Destabilizing	1.0	D	0.803	deleterious	N	0.318799794	None	None	N
K/P	0.9872	likely_pathogenic	0.9878	pathogenic	0.427	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/Q	0.4759	ambiguous	0.4071	ambiguous	-0.12	Destabilizing	1.0	D	0.819	deleterious	N	0.326004407	None	None	N
K/R	0.1396	likely_benign	0.1204	benign	-0.154	Destabilizing	0.999	D	0.623	neutral	N	0.341042165	None	None	N
K/S	0.9366	likely_pathogenic	0.9195	pathogenic	-0.506	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
K/T	0.7435	likely_pathogenic	0.7041	pathogenic	-0.288	Destabilizing	1.0	D	0.738	deleterious	N	0.330288049	None	None	N
K/V	0.8332	likely_pathogenic	0.8101	pathogenic	0.427	Stabilizing	1.0	D	0.691	prob.delet.	None	None	None	None	N
K/W	0.9788	likely_pathogenic	0.9715	pathogenic	-0.069	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/Y	0.9588	likely_pathogenic	0.9445	pathogenic	0.272	Stabilizing	1.0	D	0.753	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.