TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15428	46507;46508;46509	chr2:178620239;178620238;178620237	chr2:179484966;179484965;179484964
N2AB	13787	41584;41585;41586	chr2:178620239;178620238;178620237	chr2:179484966;179484965;179484964
N2A	12860	38803;38804;38805	chr2:178620239;178620238;178620237	chr2:179484966;179484965;179484964
N2B	6363	19312;19313;19314	chr2:178620239;178620238;178620237	chr2:179484966;179484965;179484964
Novex-1	6488	19687;19688;19689	chr2:178620239;178620238;178620237	chr2:179484966;179484965;179484964
Novex-2	6555	19888;19889;19890	chr2:178620239;178620238;178620237	chr2:179484966;179484965;179484964
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-106
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.6451
• 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
R/K	rs2058065577	None	0.997	N	0.588	0.32	0.509878532422	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.7208	likely_pathogenic	0.7456	pathogenic	0.082	Stabilizing	0.999	D	0.646	neutral	None	None	None	None	N
R/C	0.4989	ambiguous	0.4932	ambiguous	-0.13	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
R/D	0.8689	likely_pathogenic	0.8691	pathogenic	-0.151	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
R/E	0.5639	ambiguous	0.5828	pathogenic	-0.096	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
R/F	0.7779	likely_pathogenic	0.8068	pathogenic	-0.184	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
R/G	0.6423	likely_pathogenic	0.6773	pathogenic	-0.089	Destabilizing	1.0	D	0.625	neutral	D	0.576809989	None	None	N
R/H	0.2044	likely_benign	0.204	benign	-0.584	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
R/I	0.4507	ambiguous	0.4646	ambiguous	0.491	Stabilizing	1.0	D	0.718	prob.delet.	N	0.511578919	None	None	N
R/K	0.1204	likely_benign	0.1263	benign	-0.031	Destabilizing	0.997	D	0.588	neutral	N	0.482003615	None	None	N
R/L	0.4977	ambiguous	0.5255	ambiguous	0.491	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
R/M	0.4908	ambiguous	0.523	ambiguous	0.035	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
R/N	0.7684	likely_pathogenic	0.7788	pathogenic	0.114	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
R/P	0.9709	likely_pathogenic	0.9757	pathogenic	0.374	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
R/Q	0.171	likely_benign	0.1774	benign	0.051	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
R/S	0.7894	likely_pathogenic	0.8153	pathogenic	-0.141	Destabilizing	1.0	D	0.677	prob.neutral	N	0.500877172	None	None	N
R/T	0.5304	ambiguous	0.5477	ambiguous	0.035	Stabilizing	1.0	D	0.669	neutral	N	0.509488873	None	None	N
R/V	0.5667	likely_pathogenic	0.5829	pathogenic	0.374	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
R/W	0.3911	ambiguous	0.4137	ambiguous	-0.313	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
R/Y	0.6589	likely_pathogenic	0.675	pathogenic	0.105	Stabilizing	1.0	D	0.688	prob.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.