TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19352	58279;58280;58281	chr2:178594440;178594439;178594438	chr2:179459167;179459166;179459165
N2AB	17711	53356;53357;53358	chr2:178594440;178594439;178594438	chr2:179459167;179459166;179459165
N2A	16784	50575;50576;50577	chr2:178594440;178594439;178594438	chr2:179459167;179459166;179459165
N2B	10287	31084;31085;31086	chr2:178594440;178594439;178594438	chr2:179459167;179459166;179459165
Novex-1	10412	31459;31460;31461	chr2:178594440;178594439;178594438	chr2:179459167;179459166;179459165
Novex-2	10479	31660;31661;31662	chr2:178594440;178594439;178594438	chr2:179459167;179459166;179459165
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-28
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.3511
• 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
G/D	rs995136716	None	1.0	N	0.793	0.428	0.367992661779	gnomAD-4.0.0	6.8451E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99692E-07	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
G/A	0.5336	ambiguous	0.4776	ambiguous	-0.444	Destabilizing	1.0	D	0.704	prob.neutral	N	0.487242357	None	None	N
G/C	0.6988	likely_pathogenic	0.6593	pathogenic	-0.863	Destabilizing	1.0	D	0.78	deleterious	D	0.549672651	None	None	N
G/D	0.4951	ambiguous	0.4153	ambiguous	-0.935	Destabilizing	1.0	D	0.793	deleterious	N	0.48030337	None	None	N
G/E	0.6703	likely_pathogenic	0.5827	pathogenic	-1.099	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
G/F	0.92	likely_pathogenic	0.8999	pathogenic	-1.171	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
G/H	0.8429	likely_pathogenic	0.7992	pathogenic	-0.719	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/I	0.9324	likely_pathogenic	0.9097	pathogenic	-0.526	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
G/K	0.8716	likely_pathogenic	0.8294	pathogenic	-0.955	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/L	0.8685	likely_pathogenic	0.8387	pathogenic	-0.526	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/M	0.8615	likely_pathogenic	0.8272	pathogenic	-0.386	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/N	0.3741	ambiguous	0.3339	benign	-0.572	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/P	0.9963	likely_pathogenic	0.9954	pathogenic	-0.464	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/Q	0.7852	likely_pathogenic	0.7249	pathogenic	-0.918	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/R	0.8424	likely_pathogenic	0.7905	pathogenic	-0.436	Destabilizing	1.0	D	0.823	deleterious	N	0.516311297	None	None	N
G/S	0.311	likely_benign	0.2769	benign	-0.701	Destabilizing	1.0	D	0.768	deleterious	N	0.490507586	None	None	N
G/T	0.5868	likely_pathogenic	0.5379	ambiguous	-0.807	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
G/V	0.8697	likely_pathogenic	0.8307	pathogenic	-0.464	Destabilizing	1.0	D	0.799	deleterious	N	0.514932172	None	None	N
G/W	0.8697	likely_pathogenic	0.8298	pathogenic	-1.319	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
G/Y	0.8385	likely_pathogenic	0.8011	pathogenic	-0.977	Destabilizing	1.0	D	0.775	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.