TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19899	59920;59921;59922	chr2:178592209;178592208;178592207	chr2:179456936;179456935;179456934
N2AB	18258	54997;54998;54999	chr2:178592209;178592208;178592207	chr2:179456936;179456935;179456934
N2A	17331	52216;52217;52218	chr2:178592209;178592208;178592207	chr2:179456936;179456935;179456934
N2B	10834	32725;32726;32727	chr2:178592209;178592208;178592207	chr2:179456936;179456935;179456934
Novex-1	10959	33100;33101;33102	chr2:178592209;178592208;178592207	chr2:179456936;179456935;179456934
Novex-2	11026	33301;33302;33303	chr2:178592209;178592208;178592207	chr2:179456936;179456935;179456934
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: Fn3-32
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4574
• 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	rs1450922913	None	0.969	N	0.523	0.335	0.294206760003	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs1450922913	None	0.969	N	0.523	0.335	0.294206760003	gnomAD-4.0.0	3.10186E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.24073E-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	0.4428	ambiguous	0.4861	ambiguous	-0.408	Destabilizing	0.953	D	0.595	neutral	None	None	None	None	N
K/C	0.7325	likely_pathogenic	0.754	pathogenic	-0.39	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
K/D	0.629	likely_pathogenic	0.6813	pathogenic	-0.159	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
K/E	0.2164	likely_benign	0.236	benign	-0.08	Destabilizing	0.969	D	0.523	neutral	N	0.474920026	None	None	N
K/F	0.8976	likely_pathogenic	0.9032	pathogenic	-0.11	Destabilizing	0.986	D	0.78	deleterious	None	None	None	None	N
K/G	0.5295	ambiguous	0.57	pathogenic	-0.75	Destabilizing	0.993	D	0.697	prob.neutral	None	None	None	None	N
K/H	0.3793	ambiguous	0.3928	ambiguous	-1.082	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
K/I	0.5959	likely_pathogenic	0.6046	pathogenic	0.464	Stabilizing	0.964	D	0.771	deleterious	N	0.470282829	None	None	N
K/L	0.5231	ambiguous	0.5254	ambiguous	0.464	Stabilizing	0.778	D	0.585	neutral	None	None	None	None	N
K/M	0.3451	ambiguous	0.3488	ambiguous	0.338	Stabilizing	0.807	D	0.415	neutral	None	None	None	None	N
K/N	0.482	ambiguous	0.5056	ambiguous	-0.306	Destabilizing	0.997	D	0.658	neutral	N	0.488678757	None	None	N
K/P	0.9682	likely_pathogenic	0.9761	pathogenic	0.204	Stabilizing	0.998	D	0.778	deleterious	None	None	None	None	N
K/Q	0.1425	likely_benign	0.1473	benign	-0.426	Destabilizing	0.991	D	0.635	neutral	N	0.493719217	None	None	N
K/R	0.0875	likely_benign	0.0917	benign	-0.579	Destabilizing	0.969	D	0.532	neutral	N	0.518924306	None	None	N
K/S	0.481	ambiguous	0.521	ambiguous	-0.894	Destabilizing	0.976	D	0.585	neutral	None	None	None	None	N
K/T	0.2663	likely_benign	0.2958	benign	-0.628	Destabilizing	0.982	D	0.743	deleterious	N	0.491697632	None	None	N
K/V	0.5056	ambiguous	0.5237	ambiguous	0.204	Stabilizing	0.91	D	0.662	neutral	None	None	None	None	N
K/W	0.8533	likely_pathogenic	0.8598	pathogenic	0.001	Stabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
K/Y	0.7806	likely_pathogenic	0.7923	pathogenic	0.264	Stabilizing	0.993	D	0.784	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.