TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19294	58105;58106;58107	chr2:178594614;178594613;178594612	chr2:179459341;179459340;179459339
N2AB	17653	53182;53183;53184	chr2:178594614;178594613;178594612	chr2:179459341;179459340;179459339
N2A	16726	50401;50402;50403	chr2:178594614;178594613;178594612	chr2:179459341;179459340;179459339
N2B	10229	30910;30911;30912	chr2:178594614;178594613;178594612	chr2:179459341;179459340;179459339
Novex-1	10354	31285;31286;31287	chr2:178594614;178594613;178594612	chr2:179459341;179459340;179459339
Novex-2	10421	31486;31487;31488	chr2:178594614;178594613;178594612	chr2:179459341;179459340;179459339
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: Fn3-28
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.4783
• 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	None	None	0.007	N	0.123	0.037	0.0551355673512	gnomAD-4.0.0	1.5964E-06	None	None	None	None	N	None	0	2.294E-05	None	0	0	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	0.2343	likely_benign	0.2617	benign	-0.126	Destabilizing	0.373	N	0.327	neutral	None	None	None	None	N
K/C	0.5958	likely_pathogenic	0.6294	pathogenic	-0.244	Destabilizing	0.996	D	0.373	neutral	None	None	None	None	N
K/D	0.499	ambiguous	0.5642	pathogenic	0.15	Stabilizing	0.59	D	0.389	neutral	None	None	None	None	N
K/E	0.1298	likely_benign	0.1396	benign	0.198	Stabilizing	0.472	N	0.455	neutral	N	0.415103718	None	None	N
K/F	0.7209	likely_pathogenic	0.737	pathogenic	-0.043	Destabilizing	0.953	D	0.412	neutral	None	None	None	None	N
K/G	0.3997	ambiguous	0.4492	ambiguous	-0.408	Destabilizing	0.373	N	0.37	neutral	None	None	None	None	N
K/H	0.2994	likely_benign	0.3262	benign	-0.679	Destabilizing	0.953	D	0.398	neutral	None	None	None	None	N
K/I	0.2369	likely_benign	0.2494	benign	0.561	Stabilizing	0.884	D	0.415	neutral	N	0.428995735	None	None	N
K/L	0.2607	likely_benign	0.2889	benign	0.561	Stabilizing	0.59	D	0.399	neutral	None	None	None	None	N
K/M	0.1655	likely_benign	0.1752	benign	0.322	Stabilizing	0.984	D	0.399	neutral	None	None	None	None	N
K/N	0.3413	ambiguous	0.3993	ambiguous	0.077	Stabilizing	0.007	N	0.123	neutral	N	0.464167101	None	None	N
K/P	0.8761	likely_pathogenic	0.8865	pathogenic	0.363	Stabilizing	0.854	D	0.442	neutral	None	None	None	None	N
K/Q	0.1184	likely_benign	0.1195	benign	-0.063	Destabilizing	0.684	D	0.475	neutral	N	0.454470183	None	None	N
K/R	0.0963	likely_benign	0.0931	benign	-0.213	Destabilizing	0.684	D	0.438	neutral	N	0.460241362	None	None	N
K/S	0.2997	likely_benign	0.3378	benign	-0.493	Destabilizing	0.101	N	0.099	neutral	None	None	None	None	N
K/T	0.0858	likely_benign	0.0944	benign	-0.271	Destabilizing	0.004	N	0.105	neutral	N	0.373851741	None	None	N
K/V	0.1993	likely_benign	0.2176	benign	0.363	Stabilizing	0.59	D	0.405	neutral	None	None	None	None	N
K/W	0.7672	likely_pathogenic	0.7724	pathogenic	0.018	Stabilizing	0.996	D	0.431	neutral	None	None	None	None	N
K/Y	0.6327	likely_pathogenic	0.6508	pathogenic	0.325	Stabilizing	0.984	D	0.399	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.