TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27430	82513;82514;82515	chr2:178563844;178563843;178563842	chr2:179428571;179428570;179428569
N2AB	25789	77590;77591;77592	chr2:178563844;178563843;178563842	chr2:179428571;179428570;179428569
N2A	24862	74809;74810;74811	chr2:178563844;178563843;178563842	chr2:179428571;179428570;179428569
N2B	18365	55318;55319;55320	chr2:178563844;178563843;178563842	chr2:179428571;179428570;179428569
Novex-1	18490	55693;55694;55695	chr2:178563844;178563843;178563842	chr2:179428571;179428570;179428569
Novex-2	18557	55894;55895;55896	chr2:178563844;178563843;178563842	chr2:179428571;179428570;179428569
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: Fn3-87
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.184
• 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	1.0	N	0.73	0.308	0.191931220699	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	2.775E-05	None	0	0	0	0	0
K/R	None	None	0.999	N	0.514	0.336	0.243398259712	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.8248	likely_pathogenic	0.7884	pathogenic	-0.736	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
K/C	0.8876	likely_pathogenic	0.8782	pathogenic	-0.675	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
K/D	0.9596	likely_pathogenic	0.9574	pathogenic	-0.272	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/E	0.7705	likely_pathogenic	0.7385	pathogenic	-0.123	Destabilizing	0.999	D	0.551	neutral	N	0.489273403	None	None	N
K/F	0.9712	likely_pathogenic	0.9699	pathogenic	-0.334	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
K/G	0.9102	likely_pathogenic	0.8948	pathogenic	-1.098	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/H	0.642	likely_pathogenic	0.6217	pathogenic	-1.139	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
K/I	0.7508	likely_pathogenic	0.738	pathogenic	0.215	Stabilizing	1.0	D	0.905	deleterious	N	0.512150262	None	None	N
K/L	0.7887	likely_pathogenic	0.7645	pathogenic	0.215	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/M	0.6417	likely_pathogenic	0.5878	pathogenic	-0.141	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
K/N	0.9193	likely_pathogenic	0.9043	pathogenic	-0.627	Destabilizing	1.0	D	0.73	prob.delet.	N	0.467975411	None	None	N
K/P	0.9157	likely_pathogenic	0.9079	pathogenic	-0.074	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
K/Q	0.4483	ambiguous	0.4032	ambiguous	-0.565	Destabilizing	1.0	D	0.697	prob.neutral	N	0.501645267	None	None	N
K/R	0.1058	likely_benign	0.1067	benign	-0.463	Destabilizing	0.999	D	0.514	neutral	N	0.471285075	None	None	N
K/S	0.8845	likely_pathogenic	0.8579	pathogenic	-1.208	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
K/T	0.5747	likely_pathogenic	0.5163	ambiguous	-0.848	Destabilizing	1.0	D	0.802	deleterious	N	0.395338947	None	None	N
K/V	0.6872	likely_pathogenic	0.6651	pathogenic	-0.074	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
K/W	0.9311	likely_pathogenic	0.9358	pathogenic	-0.271	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
K/Y	0.9107	likely_pathogenic	0.9053	pathogenic	-0.008	Destabilizing	1.0	D	0.873	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.