TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18409	55450;55451;55452	chr2:178602046;178602045;178602044	chr2:179466773;179466772;179466771
N2AB	16768	50527;50528;50529	chr2:178602046;178602045;178602044	chr2:179466773;179466772;179466771
N2A	15841	47746;47747;47748	chr2:178602046;178602045;178602044	chr2:179466773;179466772;179466771
N2B	9344	28255;28256;28257	chr2:178602046;178602045;178602044	chr2:179466773;179466772;179466771
Novex-1	9469	28630;28631;28632	chr2:178602046;178602045;178602044	chr2:179466773;179466772;179466771
Novex-2	9536	28831;28832;28833	chr2:178602046;178602045;178602044	chr2:179466773;179466772;179466771
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-115
• Domain position: 28
• Structural Position: 45
• Q(SASA): 0.5173
• 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	None	None	0.928	N	0.538	0.29	0.356484672536	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	3.66327E-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	0.3104	likely_benign	0.3128	benign	0.004	Stabilizing	0.944	D	0.605	neutral	None	None	None	None	N
K/C	0.6479	likely_pathogenic	0.6785	pathogenic	-0.212	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
K/D	0.614	likely_pathogenic	0.6418	pathogenic	0.208	Stabilizing	0.983	D	0.73	prob.delet.	None	None	None	None	N
K/E	0.1964	likely_benign	0.2033	benign	0.222	Stabilizing	0.928	D	0.538	neutral	N	0.449382155	None	None	N
K/F	0.7095	likely_pathogenic	0.7273	pathogenic	-0.191	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
K/G	0.5156	ambiguous	0.5243	ambiguous	-0.202	Destabilizing	0.983	D	0.628	neutral	None	None	None	None	N
K/H	0.3283	likely_benign	0.3349	benign	-0.503	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
K/I	0.2529	likely_benign	0.2585	benign	0.469	Stabilizing	0.989	D	0.747	deleterious	N	0.515359218	None	None	N
K/L	0.3459	ambiguous	0.3472	ambiguous	0.469	Stabilizing	0.983	D	0.628	neutral	None	None	None	None	N
K/M	0.249	likely_benign	0.255	benign	0.235	Stabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
K/N	0.4457	ambiguous	0.4703	ambiguous	0.237	Stabilizing	0.978	D	0.651	neutral	N	0.500928483	None	None	N
K/P	0.8496	likely_pathogenic	0.858	pathogenic	0.343	Stabilizing	0.997	D	0.741	deleterious	None	None	None	None	N
K/Q	0.1388	likely_benign	0.1395	benign	0.087	Stabilizing	0.978	D	0.636	neutral	N	0.492615644	None	None	N
K/R	0.0879	likely_benign	0.0901	benign	-0.051	Destabilizing	0.085	N	0.279	neutral	N	0.519340885	None	None	N
K/S	0.3916	ambiguous	0.3991	ambiguous	-0.273	Destabilizing	0.944	D	0.609	neutral	None	None	None	None	N
K/T	0.1482	likely_benign	0.1521	benign	-0.104	Destabilizing	0.978	D	0.689	prob.neutral	N	0.469354782	None	None	N
K/V	0.2188	likely_benign	0.225	benign	0.343	Stabilizing	0.992	D	0.73	prob.delet.	None	None	None	None	N
K/W	0.7845	likely_pathogenic	0.7942	pathogenic	-0.205	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
K/Y	0.6277	likely_pathogenic	0.6474	pathogenic	0.154	Stabilizing	0.997	D	0.736	prob.delet.	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.