TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17138	51637;51638;51639	chr2:178610114;178610113;178610112	chr2:179474841;179474840;179474839
N2AB	15497	46714;46715;46716	chr2:178610114;178610113;178610112	chr2:179474841;179474840;179474839
N2A	14570	43933;43934;43935	chr2:178610114;178610113;178610112	chr2:179474841;179474840;179474839
N2B	8073	24442;24443;24444	chr2:178610114;178610113;178610112	chr2:179474841;179474840;179474839
Novex-1	8198	24817;24818;24819	chr2:178610114;178610113;178610112	chr2:179474841;179474840;179474839
Novex-2	8265	25018;25019;25020	chr2:178610114;178610113;178610112	chr2:179474841;179474840;179474839
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-12
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.2836
• 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
P/R	None	None	1.0	N	0.921	0.379	0.486993258117	gnomAD-4.0.0	1.5933E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02975E-05
P/S	None	None	1.0	N	0.894	0.298	0.377799810692	gnomAD-4.0.0	1.59327E-06	None	None	None	None	N	None	0	0	None	0	2.78598E-05	None	0	0	0	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
P/A	0.1948	likely_benign	0.2823	benign	-1.119	Destabilizing	0.999	D	0.839	deleterious	N	0.486419525	None	None	N
P/C	0.894	likely_pathogenic	0.9359	pathogenic	-0.693	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/D	0.9667	likely_pathogenic	0.9804	pathogenic	-0.662	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/E	0.895	likely_pathogenic	0.9464	pathogenic	-0.654	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/F	0.98	likely_pathogenic	0.989	pathogenic	-0.773	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/G	0.7745	likely_pathogenic	0.831	pathogenic	-1.428	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
P/H	0.8278	likely_pathogenic	0.9035	pathogenic	-0.88	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/I	0.8964	likely_pathogenic	0.9405	pathogenic	-0.38	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/K	0.9226	likely_pathogenic	0.9599	pathogenic	-0.888	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/L	0.7571	likely_pathogenic	0.8514	pathogenic	-0.38	Destabilizing	1.0	D	0.905	deleterious	N	0.483438517	None	None	N
P/M	0.8843	likely_pathogenic	0.9326	pathogenic	-0.359	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/N	0.911	likely_pathogenic	0.9504	pathogenic	-0.689	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
P/Q	0.7775	likely_pathogenic	0.8843	pathogenic	-0.8	Destabilizing	1.0	D	0.911	deleterious	N	0.496315759	None	None	N
P/R	0.8115	likely_pathogenic	0.89	pathogenic	-0.448	Destabilizing	1.0	D	0.921	deleterious	N	0.462335748	None	None	N
P/S	0.5336	ambiguous	0.6752	pathogenic	-1.223	Destabilizing	1.0	D	0.894	deleterious	N	0.514184916	None	None	N
P/T	0.5425	ambiguous	0.6911	pathogenic	-1.095	Destabilizing	1.0	D	0.889	deleterious	N	0.465841241	None	None	N
P/V	0.76	likely_pathogenic	0.8408	pathogenic	-0.59	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/W	0.9884	likely_pathogenic	0.9929	pathogenic	-0.96	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/Y	0.9705	likely_pathogenic	0.9835	pathogenic	-0.648	Destabilizing	1.0	D	0.903	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.