TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30229	90910;90911;90912	chr2:178552215;178552214;178552213	chr2:179416942;179416941;179416940
N2AB	28588	85987;85988;85989	chr2:178552215;178552214;178552213	chr2:179416942;179416941;179416940
N2A	27661	83206;83207;83208	chr2:178552215;178552214;178552213	chr2:179416942;179416941;179416940
N2B	21164	63715;63716;63717	chr2:178552215;178552214;178552213	chr2:179416942;179416941;179416940
Novex-1	21289	64090;64091;64092	chr2:178552215;178552214;178552213	chr2:179416942;179416941;179416940
Novex-2	21356	64291;64292;64293	chr2:178552215;178552214;178552213	chr2:179416942;179416941;179416940
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: Fn3-108
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.4052
• 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	rs1311556437	-0.223	0.986	N	0.524	0.201	0.402899589544	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
K/E	rs1311556437	-0.223	0.986	N	0.524	0.201	0.402899589544	gnomAD-4.0.0	6.15936E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19672E-06	0	1.65711E-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	0.1837	likely_benign	0.2071	benign	-0.167	Destabilizing	0.863	D	0.453	neutral	None	None	None	None	N
K/C	0.4224	ambiguous	0.4975	ambiguous	-0.274	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
K/D	0.5652	likely_pathogenic	0.6201	pathogenic	0.023	Stabilizing	0.997	D	0.547	neutral	None	None	None	None	N
K/E	0.1452	likely_benign	0.1612	benign	0.093	Stabilizing	0.986	D	0.524	neutral	N	0.436052206	None	None	N
K/F	0.63	likely_pathogenic	0.6954	pathogenic	0.011	Stabilizing	0.991	D	0.601	neutral	None	None	None	None	N
K/G	0.3229	likely_benign	0.361	ambiguous	-0.477	Destabilizing	0.99	D	0.528	neutral	None	None	None	None	N
K/H	0.2874	likely_benign	0.3256	benign	-0.781	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	N
K/I	0.175	likely_benign	0.2039	benign	0.607	Stabilizing	0.134	N	0.426	neutral	N	0.492828209	None	None	N
K/L	0.2244	likely_benign	0.2583	benign	0.607	Stabilizing	0.759	D	0.442	neutral	None	None	None	None	N
K/M	0.1552	likely_benign	0.1697	benign	0.311	Stabilizing	0.991	D	0.523	neutral	None	None	None	None	N
K/N	0.3421	ambiguous	0.3759	ambiguous	-0.075	Destabilizing	0.996	D	0.527	neutral	N	0.469260703	None	None	N
K/P	0.8213	likely_pathogenic	0.8452	pathogenic	0.38	Stabilizing	0.997	D	0.555	neutral	None	None	None	None	N
K/Q	0.1076	likely_benign	0.1213	benign	-0.156	Destabilizing	0.996	D	0.523	neutral	N	0.419351957	None	None	N
K/R	0.0711	likely_benign	0.0775	benign	-0.366	Destabilizing	0.986	D	0.519	neutral	N	0.434070694	None	None	N
K/S	0.2663	likely_benign	0.3081	benign	-0.607	Destabilizing	0.969	D	0.503	neutral	None	None	None	None	N
K/T	0.095	likely_benign	0.1023	benign	-0.354	Destabilizing	0.92	D	0.49	neutral	N	0.393589508	None	None	N
K/V	0.1364	likely_benign	0.1655	benign	0.38	Stabilizing	0.079	N	0.397	neutral	None	None	None	None	N
K/W	0.7517	likely_pathogenic	0.8021	pathogenic	0.053	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	N
K/Y	0.5767	likely_pathogenic	0.6322	pathogenic	0.352	Stabilizing	0.997	D	0.579	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.