TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13823	41692;41693;41694	chr2:178636104;178636103;178636102	chr2:179500831;179500830;179500829
N2AB	12182	36769;36770;36771	chr2:178636104;178636103;178636102	chr2:179500831;179500830;179500829
N2A	11255	33988;33989;33990	chr2:178636104;178636103;178636102	chr2:179500831;179500830;179500829
N2B	4758	14497;14498;14499	chr2:178636104;178636103;178636102	chr2:179500831;179500830;179500829
Novex-1	4883	14872;14873;14874	chr2:178636104;178636103;178636102	chr2:179500831;179500830;179500829
Novex-2	4950	15073;15074;15075	chr2:178636104;178636103;178636102	chr2:179500831;179500830;179500829
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-88
• Domain position: 44
• Structural Position: 74
• Q(SASA): 0.5634
• 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	rs2060403983	None	0.627	N	0.451	0.226	0.273503213844	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
P/A	0.067	likely_benign	0.1007	benign	-0.354	Destabilizing	None	N	0.103	neutral	N	0.352125352	None	None	N
P/C	0.6339	likely_pathogenic	0.8186	pathogenic	-0.743	Destabilizing	0.944	D	0.378	neutral	None	None	None	None	N
P/D	0.3722	ambiguous	0.569	pathogenic	-0.453	Destabilizing	0.002	N	0.188	neutral	None	None	None	None	N
P/E	0.2198	likely_benign	0.3633	ambiguous	-0.572	Destabilizing	0.241	N	0.349	neutral	None	None	None	None	N
P/F	0.6012	likely_pathogenic	0.8239	pathogenic	-0.679	Destabilizing	0.818	D	0.427	neutral	None	None	None	None	N
P/G	0.3187	likely_benign	0.5092	ambiguous	-0.44	Destabilizing	0.116	N	0.334	neutral	None	None	None	None	N
P/H	0.2307	likely_benign	0.378	ambiguous	-0.021	Destabilizing	0.975	D	0.318	neutral	N	0.331228996	None	None	N
P/I	0.3425	ambiguous	0.5335	ambiguous	-0.278	Destabilizing	0.69	D	0.545	neutral	None	None	None	None	N
P/K	0.2575	likely_benign	0.4405	ambiguous	-0.462	Destabilizing	0.388	N	0.353	neutral	None	None	None	None	N
P/L	0.144	likely_benign	0.2358	benign	-0.278	Destabilizing	0.193	N	0.449	neutral	N	0.339829317	None	None	N
P/M	0.3417	ambiguous	0.5132	ambiguous	-0.489	Destabilizing	0.944	D	0.317	neutral	None	None	None	None	N
P/N	0.3061	likely_benign	0.4993	ambiguous	-0.248	Destabilizing	0.388	N	0.452	neutral	None	None	None	None	N
P/Q	0.1511	likely_benign	0.258	benign	-0.484	Destabilizing	0.818	D	0.428	neutral	None	None	None	None	N
P/R	0.1972	likely_benign	0.33	benign	0.044	Stabilizing	0.627	D	0.451	neutral	N	0.319740092	None	None	N
P/S	0.1268	likely_benign	0.2222	benign	-0.542	Destabilizing	0.006	N	0.205	neutral	N	0.347821801	None	None	N
P/T	0.1031	likely_benign	0.1742	benign	-0.568	Destabilizing	0.193	N	0.349	neutral	N	0.342470837	None	None	N
P/V	0.2367	likely_benign	0.3729	ambiguous	-0.272	Destabilizing	0.241	N	0.386	neutral	None	None	None	None	N
P/W	0.7395	likely_pathogenic	0.9013	pathogenic	-0.753	Destabilizing	0.981	D	0.468	neutral	None	None	None	None	N
P/Y	0.5296	ambiguous	0.7488	pathogenic	-0.468	Destabilizing	0.932	D	0.421	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.