TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16216	48871;48872;48873	chr2:178614961;178614960;178614959	chr2:179479688;179479687;179479686
N2AB	14575	43948;43949;43950	chr2:178614961;178614960;178614959	chr2:179479688;179479687;179479686
N2A	13648	41167;41168;41169	chr2:178614961;178614960;178614959	chr2:179479688;179479687;179479686
N2B	7151	21676;21677;21678	chr2:178614961;178614960;178614959	chr2:179479688;179479687;179479686
Novex-1	7276	22051;22052;22053	chr2:178614961;178614960;178614959	chr2:179479688;179479687;179479686
Novex-2	7343	22252;22253;22254	chr2:178614961;178614960;178614959	chr2:179479688;179479687;179479686
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-5
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.118
• 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
V/A	None	None	0.998	D	0.638	0.5	0.552005039658	gnomAD-4.0.0	1.6308E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.925E-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
V/A	0.6632	likely_pathogenic	0.6935	pathogenic	-2.138	Highly Destabilizing	0.998	D	0.638	neutral	D	0.581343766	None	None	N
V/C	0.9184	likely_pathogenic	0.9291	pathogenic	-1.75	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/D	0.9667	likely_pathogenic	0.9678	pathogenic	-2.462	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/E	0.9212	likely_pathogenic	0.9277	pathogenic	-2.241	Highly Destabilizing	1.0	D	0.803	deleterious	D	0.720621124	None	None	N
V/F	0.6968	likely_pathogenic	0.725	pathogenic	-1.29	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
V/G	0.8367	likely_pathogenic	0.8423	pathogenic	-2.695	Highly Destabilizing	1.0	D	0.821	deleterious	D	0.775329474	None	None	N
V/H	0.9826	likely_pathogenic	0.9849	pathogenic	-2.335	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/I	0.1101	likely_benign	0.1122	benign	-0.588	Destabilizing	0.813	D	0.263	neutral	None	None	None	None	N
V/K	0.9622	likely_pathogenic	0.9623	pathogenic	-1.864	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/L	0.6204	likely_pathogenic	0.6701	pathogenic	-0.588	Destabilizing	0.981	D	0.628	neutral	N	0.516716889	None	None	N
V/M	0.5549	ambiguous	0.6002	pathogenic	-0.627	Destabilizing	0.999	D	0.768	deleterious	D	0.64274311	None	None	N
V/N	0.9308	likely_pathogenic	0.9386	pathogenic	-2.147	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/P	0.9868	likely_pathogenic	0.9838	pathogenic	-1.076	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/Q	0.9432	likely_pathogenic	0.9506	pathogenic	-1.986	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/R	0.9572	likely_pathogenic	0.9576	pathogenic	-1.684	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/S	0.8955	likely_pathogenic	0.9083	pathogenic	-2.83	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
V/T	0.8044	likely_pathogenic	0.8203	pathogenic	-2.446	Highly Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
V/W	0.993	likely_pathogenic	0.9937	pathogenic	-1.729	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9477	likely_pathogenic	0.9545	pathogenic	-1.361	Destabilizing	1.0	D	0.781	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.