TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19932	60019;60020;60021	chr2:178592110;178592109;178592108	chr2:179456837;179456836;179456835
N2AB	18291	55096;55097;55098	chr2:178592110;178592109;178592108	chr2:179456837;179456836;179456835
N2A	17364	52315;52316;52317	chr2:178592110;178592109;178592108	chr2:179456837;179456836;179456835
N2B	10867	32824;32825;32826	chr2:178592110;178592109;178592108	chr2:179456837;179456836;179456835
Novex-1	10992	33199;33200;33201	chr2:178592110;178592109;178592108	chr2:179456837;179456836;179456835
Novex-2	11059	33400;33401;33402	chr2:178592110;178592109;178592108	chr2:179456837;179456836;179456835
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-32
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.6116
• 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/T	None	None	1.0	N	0.661	0.395	0.378322506985	gnomAD-4.0.0	1.36903E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15958E-05	1.65766E-05

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	0.7714	likely_pathogenic	0.8137	pathogenic	-0.11	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
K/C	0.9032	likely_pathogenic	0.9116	pathogenic	-0.232	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
K/D	0.9079	likely_pathogenic	0.9278	pathogenic	0.202	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	N
K/E	0.6291	likely_pathogenic	0.6765	pathogenic	0.212	Stabilizing	0.999	D	0.605	neutral	N	0.496199375	None	None	N
K/F	0.958	likely_pathogenic	0.9666	pathogenic	-0.322	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
K/G	0.7712	likely_pathogenic	0.7948	pathogenic	-0.322	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	N
K/H	0.6516	likely_pathogenic	0.6793	pathogenic	-0.683	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
K/I	0.7952	likely_pathogenic	0.8347	pathogenic	0.368	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/L	0.7286	likely_pathogenic	0.7754	pathogenic	0.368	Stabilizing	1.0	D	0.596	neutral	None	None	None	None	N
K/M	0.6642	likely_pathogenic	0.7112	pathogenic	0.272	Stabilizing	1.0	D	0.645	neutral	N	0.496803647	None	None	N
K/N	0.8532	likely_pathogenic	0.8821	pathogenic	0.213	Stabilizing	1.0	D	0.709	prob.delet.	N	0.510878039	None	None	N
K/P	0.8067	likely_pathogenic	0.8254	pathogenic	0.237	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/Q	0.3438	ambiguous	0.3708	ambiguous	0.014	Stabilizing	1.0	D	0.69	prob.neutral	N	0.495852658	None	None	N
K/R	0.0974	likely_benign	0.0969	benign	-0.082	Destabilizing	0.999	D	0.551	neutral	N	0.478307047	None	None	N
K/S	0.8104	likely_pathogenic	0.8477	pathogenic	-0.346	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
K/T	0.5721	likely_pathogenic	0.6509	pathogenic	-0.179	Destabilizing	1.0	D	0.661	neutral	N	0.482651288	None	None	N
K/V	0.7236	likely_pathogenic	0.7667	pathogenic	0.237	Stabilizing	1.0	D	0.622	neutral	None	None	None	None	N
K/W	0.9255	likely_pathogenic	0.9297	pathogenic	-0.288	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/Y	0.9006	likely_pathogenic	0.9152	pathogenic	0.067	Stabilizing	1.0	D	0.63	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.