TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5888	17887;17888;17889	chr2:178731003;178731002;178731001	chr2:179595730;179595729;179595728
N2AB	5571	16936;16937;16938	chr2:178731003;178731002;178731001	chr2:179595730;179595729;179595728
N2A	4644	14155;14156;14157	chr2:178731003;178731002;178731001	chr2:179595730;179595729;179595728
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-42
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.3615
• 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
K/Q	rs1176630529	0.198	None	N	0.218	0.076	0.0846915920261	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/Q	rs1176630529	0.198	None	N	0.218	0.076	0.0846915920261	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43361E-05	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
K/A	0.1138	likely_benign	0.1337	benign	0.01	Stabilizing	0.016	N	0.279	neutral	None	None	None	None	N
K/C	0.4447	ambiguous	0.5016	ambiguous	-0.148	Destabilizing	0.864	D	0.263	neutral	None	None	None	None	N
K/D	0.1728	likely_benign	0.2211	benign	0.069	Stabilizing	0.038	N	0.293	neutral	None	None	None	None	N
K/E	0.0678	likely_benign	0.0906	benign	0.076	Stabilizing	0.012	N	0.304	neutral	N	0.364948964	None	None	N
K/F	0.4553	ambiguous	0.5371	ambiguous	-0.186	Destabilizing	0.356	N	0.287	neutral	None	None	None	None	N
K/G	0.1399	likely_benign	0.1651	benign	-0.193	Destabilizing	0.016	N	0.28	neutral	None	None	None	None	N
K/H	0.1839	likely_benign	0.1994	benign	-0.435	Destabilizing	0.214	N	0.265	neutral	None	None	None	None	N
K/I	0.1572	likely_benign	0.2195	benign	0.469	Stabilizing	0.171	N	0.322	neutral	N	0.4445114	None	None	N
K/L	0.1478	likely_benign	0.1839	benign	0.469	Stabilizing	0.038	N	0.312	neutral	None	None	None	None	N
K/M	0.1017	likely_benign	0.1213	benign	0.294	Stabilizing	0.356	N	0.269	neutral	None	None	None	None	N
K/N	0.1169	likely_benign	0.1473	benign	0.268	Stabilizing	0.001	N	0.169	neutral	N	0.403086065	None	None	N
K/P	0.337	likely_benign	0.3916	ambiguous	0.344	Stabilizing	0.136	N	0.351	neutral	None	None	None	None	N
K/Q	0.0787	likely_benign	0.0872	benign	0.081	Stabilizing	None	N	0.218	neutral	N	0.376400896	None	None	N
K/R	0.0759	likely_benign	0.0783	benign	0.021	Stabilizing	None	N	0.104	neutral	N	0.42003703	None	None	N
K/S	0.1207	likely_benign	0.15	benign	-0.236	Destabilizing	None	N	0.095	neutral	None	None	None	None	N
K/T	0.0708	likely_benign	0.0853	benign	-0.08	Destabilizing	None	N	0.193	neutral	N	0.384847021	None	None	N
K/V	0.1529	likely_benign	0.2	benign	0.344	Stabilizing	0.038	N	0.309	neutral	None	None	None	None	N
K/W	0.4789	ambiguous	0.5101	ambiguous	-0.193	Destabilizing	0.864	D	0.307	neutral	None	None	None	None	N
K/Y	0.3486	ambiguous	0.4102	ambiguous	0.159	Stabilizing	0.356	N	0.28	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.