TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30040	90343;90344;90345	chr2:178552782;178552781;178552780	chr2:179417509;179417508;179417507
N2AB	28399	85420;85421;85422	chr2:178552782;178552781;178552780	chr2:179417509;179417508;179417507
N2A	27472	82639;82640;82641	chr2:178552782;178552781;178552780	chr2:179417509;179417508;179417507
N2B	20975	63148;63149;63150	chr2:178552782;178552781;178552780	chr2:179417509;179417508;179417507
Novex-1	21100	63523;63524;63525	chr2:178552782;178552781;178552780	chr2:179417509;179417508;179417507
Novex-2	21167	63724;63725;63726	chr2:178552782;178552781;178552780	chr2:179417509;179417508;179417507
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: Fn3-107
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.5337
• 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	rs1322454013	0.645	0.959	N	0.36	0.184	0.244539031024	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
K/E	rs1322454013	0.645	0.959	N	0.36	0.184	0.244539031024	gnomAD-4.0.0	1.16311E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4391E-05	0	1.65645E-05
K/N	None	None	0.996	N	0.389	0.175	0.17258766438	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85794E-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	0.3599	ambiguous	0.3258	benign	-0.156	Destabilizing	0.079	N	0.132	neutral	None	None	None	None	N
K/C	0.7214	likely_pathogenic	0.6994	pathogenic	-0.221	Destabilizing	0.999	D	0.311	neutral	None	None	None	None	N
K/D	0.6641	likely_pathogenic	0.6311	pathogenic	0.105	Stabilizing	0.997	D	0.373	neutral	None	None	None	None	N
K/E	0.2003	likely_benign	0.1813	benign	0.134	Stabilizing	0.959	D	0.36	neutral	N	0.407292311	None	None	N
K/F	0.7934	likely_pathogenic	0.7741	pathogenic	-0.231	Destabilizing	0.982	D	0.36	neutral	None	None	None	None	N
K/G	0.5221	ambiguous	0.4845	ambiguous	-0.408	Destabilizing	0.939	D	0.372	neutral	None	None	None	None	N
K/H	0.3847	ambiguous	0.3679	ambiguous	-0.737	Destabilizing	0.999	D	0.34	neutral	None	None	None	None	N
K/I	0.2832	likely_benign	0.2656	benign	0.441	Stabilizing	0.704	D	0.408	neutral	N	0.423339199	None	None	N
K/L	0.3466	ambiguous	0.3313	benign	0.441	Stabilizing	0.02	N	0.192	neutral	None	None	None	None	N
K/M	0.2213	likely_benign	0.206	benign	0.309	Stabilizing	0.982	D	0.361	neutral	None	None	None	None	N
K/N	0.4525	ambiguous	0.4139	ambiguous	0.12	Stabilizing	0.996	D	0.389	neutral	N	0.475480173	None	None	N
K/P	0.8891	likely_pathogenic	0.865	pathogenic	0.272	Stabilizing	0.997	D	0.373	neutral	None	None	None	None	N
K/Q	0.1482	likely_benign	0.1392	benign	-0.055	Destabilizing	0.996	D	0.4	neutral	N	0.452045953	None	None	N
K/R	0.0885	likely_benign	0.0877	benign	-0.166	Destabilizing	0.959	D	0.389	neutral	N	0.453776749	None	None	N
K/S	0.4594	ambiguous	0.4263	ambiguous	-0.442	Destabilizing	0.884	D	0.335	neutral	None	None	None	None	N
K/T	0.1552	likely_benign	0.1441	benign	-0.245	Destabilizing	0.92	D	0.353	neutral	N	0.352841751	None	None	N
K/V	0.2723	likely_benign	0.2612	benign	0.272	Stabilizing	0.079	N	0.18	neutral	None	None	None	None	N
K/W	0.7999	likely_pathogenic	0.7769	pathogenic	-0.181	Destabilizing	0.999	D	0.383	neutral	None	None	None	None	N
K/Y	0.6941	likely_pathogenic	0.667	pathogenic	0.15	Stabilizing	0.997	D	0.349	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.