TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27480	82663;82664;82665	chr2:178563694;178563693;178563692	chr2:179428421;179428420;179428419
N2AB	25839	77740;77741;77742	chr2:178563694;178563693;178563692	chr2:179428421;179428420;179428419
N2A	24912	74959;74960;74961	chr2:178563694;178563693;178563692	chr2:179428421;179428420;179428419
N2B	18415	55468;55469;55470	chr2:178563694;178563693;178563692	chr2:179428421;179428420;179428419
Novex-1	18540	55843;55844;55845	chr2:178563694;178563693;178563692	chr2:179428421;179428420;179428419
Novex-2	18607	56044;56045;56046	chr2:178563694;178563693;178563692	chr2:179428421;179428420;179428419
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-88
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3537
• 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
A/P	rs1457913909	None	0.939	N	0.407	0.231	0.250579442822	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
A/C	0.4182	ambiguous	0.3909	ambiguous	-0.767	Destabilizing	0.996	D	0.396	neutral	None	None	None	None	N
A/D	0.4697	ambiguous	0.4036	ambiguous	-0.291	Destabilizing	0.02	N	0.295	neutral	None	None	None	None	N
A/E	0.4495	ambiguous	0.4001	ambiguous	-0.435	Destabilizing	0.521	D	0.397	neutral	N	0.421336257	None	None	N
A/F	0.3893	ambiguous	0.3447	ambiguous	-0.845	Destabilizing	0.91	D	0.489	neutral	None	None	None	None	N
A/G	0.1577	likely_benign	0.139	benign	-0.375	Destabilizing	0.521	D	0.396	neutral	N	0.492929783	None	None	N
A/H	0.5755	likely_pathogenic	0.5133	ambiguous	-0.415	Destabilizing	0.996	D	0.46	neutral	None	None	None	None	N
A/I	0.3277	likely_benign	0.2904	benign	-0.309	Destabilizing	0.02	N	0.321	neutral	None	None	None	None	N
A/K	0.6836	likely_pathogenic	0.6427	pathogenic	-0.641	Destabilizing	0.91	D	0.384	neutral	None	None	None	None	N
A/L	0.1889	likely_benign	0.1645	benign	-0.309	Destabilizing	0.59	D	0.393	neutral	None	None	None	None	N
A/M	0.2202	likely_benign	0.1929	benign	-0.363	Destabilizing	0.974	D	0.391	neutral	None	None	None	None	N
A/N	0.2277	likely_benign	0.1882	benign	-0.32	Destabilizing	0.835	D	0.455	neutral	None	None	None	None	N
A/P	0.7551	likely_pathogenic	0.7301	pathogenic	-0.272	Destabilizing	0.939	D	0.407	neutral	N	0.513651772	None	None	N
A/Q	0.4245	ambiguous	0.3888	ambiguous	-0.574	Destabilizing	0.91	D	0.421	neutral	None	None	None	None	N
A/R	0.6082	likely_pathogenic	0.5793	pathogenic	-0.213	Destabilizing	0.91	D	0.413	neutral	None	None	None	None	N
A/S	0.0931	likely_benign	0.0847	benign	-0.567	Destabilizing	0.028	N	0.186	neutral	N	0.432169326	None	None	N
A/T	0.0882	likely_benign	0.0779	benign	-0.624	Destabilizing	0.007	N	0.089	neutral	N	0.465436538	None	None	N
A/V	0.1498	likely_benign	0.1361	benign	-0.272	Destabilizing	0.521	D	0.399	neutral	N	0.517596154	None	None	N
A/W	0.8307	likely_pathogenic	0.795	pathogenic	-0.998	Destabilizing	0.996	D	0.613	neutral	None	None	None	None	N
A/Y	0.5511	ambiguous	0.5014	ambiguous	-0.644	Destabilizing	0.984	D	0.485	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.