TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21502	64729;64730;64731	chr2:178585240;178585239;178585238	chr2:179449967;179449966;179449965
N2AB	19861	59806;59807;59808	chr2:178585240;178585239;178585238	chr2:179449967;179449966;179449965
N2A	18934	57025;57026;57027	chr2:178585240;178585239;178585238	chr2:179449967;179449966;179449965
N2B	12437	37534;37535;37536	chr2:178585240;178585239;178585238	chr2:179449967;179449966;179449965
Novex-1	12562	37909;37910;37911	chr2:178585240;178585239;178585238	chr2:179449967;179449966;179449965
Novex-2	12629	38110;38111;38112	chr2:178585240;178585239;178585238	chr2:179449967;179449966;179449965
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: Ig-124
• Domain position: 34
• Structural Position: 50
• Q(SASA): 0.252
• 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	rs1199736147	-0.066	0.704	N	0.494	0.355	0.352476196916	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.67131E-04	None	0	None	0	0	0
K/E	rs1199736147	-0.066	0.704	N	0.494	0.355	0.352476196916	gnomAD-4.0.0	4.77681E-06	None	None	None	None	N	None	0	0	None	0	8.3227E-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	0.6933	likely_pathogenic	0.5941	pathogenic	-0.806	Destabilizing	0.863	D	0.463	neutral	None	None	None	None	N
K/C	0.7142	likely_pathogenic	0.633	pathogenic	-0.806	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
K/D	0.9024	likely_pathogenic	0.8655	pathogenic	0.123	Stabilizing	0.939	D	0.513	neutral	None	None	None	None	N
K/E	0.5302	ambiguous	0.442	ambiguous	0.226	Stabilizing	0.704	D	0.494	neutral	N	0.50130619	None	None	N
K/F	0.8485	likely_pathogenic	0.7908	pathogenic	-0.738	Destabilizing	0.997	D	0.583	neutral	None	None	None	None	N
K/G	0.8611	likely_pathogenic	0.8075	pathogenic	-1.135	Destabilizing	0.969	D	0.497	neutral	None	None	None	None	N
K/H	0.403	ambiguous	0.349	ambiguous	-1.523	Destabilizing	0.991	D	0.563	neutral	None	None	None	None	N
K/I	0.4696	ambiguous	0.3983	ambiguous	0.034	Stabilizing	0.996	D	0.576	neutral	N	0.488517853	None	None	N
K/L	0.4951	ambiguous	0.4091	ambiguous	0.034	Stabilizing	0.939	D	0.497	neutral	None	None	None	None	N
K/M	0.3418	ambiguous	0.2764	benign	-0.01	Destabilizing	0.997	D	0.559	neutral	None	None	None	None	N
K/N	0.7398	likely_pathogenic	0.6702	pathogenic	-0.373	Destabilizing	0.959	D	0.508	neutral	N	0.5010527	None	None	N
K/P	0.9826	likely_pathogenic	0.9763	pathogenic	-0.217	Destabilizing	0.997	D	0.553	neutral	None	None	None	None	N
K/Q	0.2291	likely_benign	0.1933	benign	-0.478	Destabilizing	0.31	N	0.189	neutral	N	0.471085161	None	None	N
K/R	0.0809	likely_benign	0.074	benign	-0.468	Destabilizing	0.015	N	0.147	neutral	N	0.430296883	None	None	N
K/S	0.7722	likely_pathogenic	0.6782	pathogenic	-1.148	Destabilizing	0.939	D	0.47	neutral	None	None	None	None	N
K/T	0.4752	ambiguous	0.3788	ambiguous	-0.831	Destabilizing	0.959	D	0.507	neutral	N	0.489278321	None	None	N
K/V	0.4649	ambiguous	0.3833	ambiguous	-0.217	Destabilizing	0.991	D	0.552	neutral	None	None	None	None	N
K/W	0.7933	likely_pathogenic	0.748	pathogenic	-0.558	Destabilizing	0.999	D	0.616	neutral	None	None	None	None	N
K/Y	0.6752	likely_pathogenic	0.6102	pathogenic	-0.242	Destabilizing	0.997	D	0.577	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.