TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22224	66895;66896;66897	chr2:178581598;178581597;178581596	chr2:179446325;179446324;179446323
N2AB	20583	61972;61973;61974	chr2:178581598;178581597;178581596	chr2:179446325;179446324;179446323
N2A	19656	59191;59192;59193	chr2:178581598;178581597;178581596	chr2:179446325;179446324;179446323
N2B	13159	39700;39701;39702	chr2:178581598;178581597;178581596	chr2:179446325;179446324;179446323
Novex-1	13284	40075;40076;40077	chr2:178581598;178581597;178581596	chr2:179446325;179446324;179446323
Novex-2	13351	40276;40277;40278	chr2:178581598;178581597;178581596	chr2:179446325;179446324;179446323
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-49
• Domain position: 69
• Structural Position: 99
• Q(SASA): 0.5055
• 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
E/K	None	None	0.978	N	0.535	0.321	0.467669411796	gnomAD-4.0.0	1.59364E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03049E-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
E/A	0.1615	likely_benign	0.174	benign	-0.463	Destabilizing	0.989	D	0.444	neutral	N	0.473379793	None	None	N
E/C	0.8884	likely_pathogenic	0.9071	pathogenic	-0.002	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/D	0.2408	likely_benign	0.2686	benign	-0.517	Destabilizing	0.054	N	0.143	neutral	D	0.525831636	None	None	N
E/F	0.8931	likely_pathogenic	0.9085	pathogenic	-0.399	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
E/G	0.2479	likely_benign	0.2615	benign	-0.693	Destabilizing	0.978	D	0.471	neutral	N	0.503680182	None	None	N
E/H	0.6792	likely_pathogenic	0.7225	pathogenic	-0.423	Destabilizing	0.999	D	0.467	neutral	None	None	None	None	N
E/I	0.5472	ambiguous	0.5718	pathogenic	0.117	Stabilizing	0.999	D	0.603	neutral	None	None	None	None	N
E/K	0.2588	likely_benign	0.2745	benign	0.106	Stabilizing	0.978	D	0.535	neutral	N	0.48233347	None	None	N
E/L	0.5782	likely_pathogenic	0.5982	pathogenic	0.117	Stabilizing	0.998	D	0.583	neutral	None	None	None	None	N
E/M	0.5907	likely_pathogenic	0.6008	pathogenic	0.359	Stabilizing	1.0	D	0.541	neutral	None	None	None	None	N
E/N	0.4238	ambiguous	0.4633	ambiguous	-0.124	Destabilizing	0.983	D	0.501	neutral	None	None	None	None	N
E/P	0.3229	likely_benign	0.343	ambiguous	-0.056	Destabilizing	0.999	D	0.458	neutral	None	None	None	None	N
E/Q	0.1966	likely_benign	0.2129	benign	-0.094	Destabilizing	0.989	D	0.547	neutral	N	0.475509841	None	None	N
E/R	0.4143	ambiguous	0.4396	ambiguous	0.254	Stabilizing	0.998	D	0.494	neutral	None	None	None	None	N
E/S	0.2897	likely_benign	0.3186	benign	-0.321	Destabilizing	0.983	D	0.486	neutral	None	None	None	None	N
E/T	0.32	likely_benign	0.3287	benign	-0.143	Destabilizing	0.992	D	0.413	neutral	None	None	None	None	N
E/V	0.3299	likely_benign	0.3474	ambiguous	-0.056	Destabilizing	0.999	D	0.495	neutral	N	0.495691238	None	None	N
E/W	0.9633	likely_pathogenic	0.9701	pathogenic	-0.272	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
E/Y	0.8327	likely_pathogenic	0.8561	pathogenic	-0.166	Destabilizing	0.999	D	0.553	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.