TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15349	46270;46271;46272	chr2:178620476;178620475;178620474	chr2:179485203;179485202;179485201
N2AB	13708	41347;41348;41349	chr2:178620476;178620475;178620474	chr2:179485203;179485202;179485201
N2A	12781	38566;38567;38568	chr2:178620476;178620475;178620474	chr2:179485203;179485202;179485201
N2B	6284	19075;19076;19077	chr2:178620476;178620475;178620474	chr2:179485203;179485202;179485201
Novex-1	6409	19450;19451;19452	chr2:178620476;178620475;178620474	chr2:179485203;179485202;179485201
Novex-2	6476	19651;19652;19653	chr2:178620476;178620475;178620474	chr2:179485203;179485202;179485201
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-105
• Domain position: 48
• Structural Position: 123
• Q(SASA): 0.1312
• 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
Y/H	rs977496032	None	1.0	D	0.765	0.553	0.476754456241	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
Y/H	rs977496032	None	1.0	D	0.765	0.553	0.476754456241	gnomAD-4.0.0	2.03037E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.2051E-06	0	3.40321E-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
Y/A	0.8232	likely_pathogenic	0.8209	pathogenic	-2.153	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
Y/C	0.2216	likely_benign	0.2333	benign	-1.484	Destabilizing	1.0	D	0.843	deleterious	D	0.600474916	None	None	N
Y/D	0.872	likely_pathogenic	0.8798	pathogenic	-2.51	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.601508465	None	None	N
Y/E	0.9379	likely_pathogenic	0.9457	pathogenic	-2.313	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/F	0.1817	likely_benign	0.1833	benign	-0.798	Destabilizing	0.999	D	0.535	neutral	N	0.507699608	None	None	N
Y/G	0.7391	likely_pathogenic	0.7482	pathogenic	-2.531	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/H	0.5151	ambiguous	0.5111	ambiguous	-1.353	Destabilizing	1.0	D	0.765	deleterious	D	0.600474916	None	None	N
Y/I	0.7083	likely_pathogenic	0.702	pathogenic	-0.921	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
Y/K	0.9065	likely_pathogenic	0.906	pathogenic	-1.838	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/L	0.5835	likely_pathogenic	0.5956	pathogenic	-0.921	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
Y/M	0.7965	likely_pathogenic	0.8106	pathogenic	-0.839	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
Y/N	0.6242	likely_pathogenic	0.6239	pathogenic	-2.648	Highly Destabilizing	1.0	D	0.856	deleterious	D	0.600474916	None	None	N
Y/P	0.9681	likely_pathogenic	0.9647	pathogenic	-1.341	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/Q	0.8456	likely_pathogenic	0.8567	pathogenic	-2.33	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
Y/R	0.8001	likely_pathogenic	0.7989	pathogenic	-1.868	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/S	0.504	ambiguous	0.492	ambiguous	-2.995	Highly Destabilizing	1.0	D	0.823	deleterious	N	0.501938569	None	None	N
Y/T	0.7756	likely_pathogenic	0.7773	pathogenic	-2.672	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/V	0.5937	likely_pathogenic	0.6017	pathogenic	-1.341	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
Y/W	0.5507	ambiguous	0.5545	ambiguous	-0.257	Destabilizing	1.0	D	0.756	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.