TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23200	69823;69824;69825	chr2:178576646;178576645;178576644	chr2:179441373;179441372;179441371
N2AB	21559	64900;64901;64902	chr2:178576646;178576645;178576644	chr2:179441373;179441372;179441371
N2A	20632	62119;62120;62121	chr2:178576646;178576645;178576644	chr2:179441373;179441372;179441371
N2B	14135	42628;42629;42630	chr2:178576646;178576645;178576644	chr2:179441373;179441372;179441371
Novex-1	14260	43003;43004;43005	chr2:178576646;178576645;178576644	chr2:179441373;179441372;179441371
Novex-2	14327	43204;43205;43206	chr2:178576646;178576645;178576644	chr2:179441373;179441372;179441371
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: Fn3-56
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.4358
• 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	rs1256094909	None	0.958	N	0.54	0.297	0.231873229951	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs1256094909	None	0.958	N	0.54	0.297	0.231873229951	gnomAD-4.0.0	6.57505E-06	None	None	None	None	N	None	2.4122E-05	0	None	0	0	None	0	0	0	0	0
K/N	None	None	0.988	N	0.681	0.279	0.17948927462	gnomAD-4.0.0	1.59158E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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	0.8845	likely_pathogenic	0.8671	pathogenic	-0.127	Destabilizing	0.968	D	0.615	neutral	None	None	None	None	N
K/C	0.9199	likely_pathogenic	0.9152	pathogenic	-0.224	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/D	0.9574	likely_pathogenic	0.9519	pathogenic	0.046	Stabilizing	0.995	D	0.749	deleterious	None	None	None	None	N
K/E	0.7851	likely_pathogenic	0.7511	pathogenic	0.062	Stabilizing	0.958	D	0.54	neutral	N	0.464492388	None	None	N
K/F	0.9734	likely_pathogenic	0.9678	pathogenic	-0.285	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/G	0.9325	likely_pathogenic	0.9307	pathogenic	-0.358	Destabilizing	0.991	D	0.681	prob.neutral	None	None	None	None	N
K/H	0.632	likely_pathogenic	0.5893	pathogenic	-0.694	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
K/I	0.7807	likely_pathogenic	0.7487	pathogenic	0.409	Stabilizing	0.994	D	0.729	prob.delet.	N	0.510803468	None	None	N
K/L	0.8105	likely_pathogenic	0.7767	pathogenic	0.409	Stabilizing	0.991	D	0.681	prob.neutral	None	None	None	None	N
K/M	0.6997	likely_pathogenic	0.6722	pathogenic	0.339	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/N	0.919	likely_pathogenic	0.9091	pathogenic	0.134	Stabilizing	0.988	D	0.681	prob.neutral	N	0.506224368	None	None	N
K/P	0.948	likely_pathogenic	0.9425	pathogenic	0.26	Stabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
K/Q	0.4888	ambiguous	0.4382	ambiguous	-0.078	Destabilizing	0.988	D	0.663	neutral	N	0.481443353	None	None	N
K/R	0.0915	likely_benign	0.0859	benign	-0.106	Destabilizing	0.142	N	0.311	neutral	N	0.420914969	None	None	N
K/S	0.9163	likely_pathogenic	0.9007	pathogenic	-0.417	Destabilizing	0.968	D	0.607	neutral	None	None	None	None	N
K/T	0.6475	likely_pathogenic	0.5946	pathogenic	-0.241	Destabilizing	0.988	D	0.741	deleterious	N	0.412577914	None	None	N
K/V	0.7352	likely_pathogenic	0.6893	pathogenic	0.26	Stabilizing	0.995	D	0.733	prob.delet.	None	None	None	None	N
K/W	0.945	likely_pathogenic	0.9369	pathogenic	-0.237	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/Y	0.9158	likely_pathogenic	0.9073	pathogenic	0.109	Stabilizing	0.998	D	0.738	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.