TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29694	89305;89306;89307	chr2:178554031;178554030;178554029	chr2:179418758;179418757;179418756
N2AB	28053	84382;84383;84384	chr2:178554031;178554030;178554029	chr2:179418758;179418757;179418756
N2A	27126	81601;81602;81603	chr2:178554031;178554030;178554029	chr2:179418758;179418757;179418756
N2B	20629	62110;62111;62112	chr2:178554031;178554030;178554029	chr2:179418758;179418757;179418756
Novex-1	20754	62485;62486;62487	chr2:178554031;178554030;178554029	chr2:179418758;179418757;179418756
Novex-2	20821	62686;62687;62688	chr2:178554031;178554030;178554029	chr2:179418758;179418757;179418756
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: Fn3-104
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.3527
• 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	rs1222832366	0.31	0.996	N	0.479	0.291	0.317084106153	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	1.11321E-04	None	0	None	0	0	0
K/E	rs1222832366	0.31	0.996	N	0.479	0.291	0.317084106153	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	None	0	0	0	0	0
K/N	None	None	0.999	N	0.668	0.18	0.144782658237	gnomAD-4.0.0	1.59139E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-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	0.7705	likely_pathogenic	0.8023	pathogenic	-0.205	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
K/C	0.8613	likely_pathogenic	0.8722	pathogenic	-0.309	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
K/D	0.9081	likely_pathogenic	0.9174	pathogenic	0.096	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/E	0.6584	likely_pathogenic	0.6934	pathogenic	0.111	Stabilizing	0.996	D	0.479	neutral	N	0.510014034	None	None	N
K/F	0.9336	likely_pathogenic	0.9477	pathogenic	-0.418	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/G	0.8804	likely_pathogenic	0.9018	pathogenic	-0.434	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/H	0.5009	ambiguous	0.5338	ambiguous	-0.833	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/I	0.5687	likely_pathogenic	0.5866	pathogenic	0.323	Stabilizing	1.0	D	0.81	deleterious	N	0.469545132	None	None	N
K/L	0.6491	likely_pathogenic	0.6783	pathogenic	0.323	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/M	0.4508	ambiguous	0.4748	ambiguous	0.329	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/N	0.7969	likely_pathogenic	0.8089	pathogenic	0.103	Stabilizing	0.999	D	0.668	neutral	N	0.521039104	None	None	N
K/P	0.9154	likely_pathogenic	0.9267	pathogenic	0.176	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/Q	0.3395	likely_benign	0.3702	ambiguous	-0.137	Destabilizing	0.999	D	0.644	neutral	N	0.466088866	None	None	N
K/R	0.097	likely_benign	0.1047	benign	-0.113	Destabilizing	0.64	D	0.372	neutral	N	0.447850855	None	None	N
K/S	0.8519	likely_pathogenic	0.87	pathogenic	-0.492	Destabilizing	0.998	D	0.586	neutral	None	None	None	None	N
K/T	0.4521	ambiguous	0.4685	ambiguous	-0.314	Destabilizing	0.999	D	0.765	deleterious	N	0.436281493	None	None	N
K/V	0.5458	ambiguous	0.5628	ambiguous	0.176	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/W	0.8887	likely_pathogenic	0.9112	pathogenic	-0.342	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
K/Y	0.8172	likely_pathogenic	0.838	pathogenic	0.017	Stabilizing	1.0	D	0.817	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.