TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13888	41887;41888;41889	chr2:178635662;178635661;178635660	chr2:179500389;179500388;179500387
N2AB	12247	36964;36965;36966	chr2:178635662;178635661;178635660	chr2:179500389;179500388;179500387
N2A	11320	34183;34184;34185	chr2:178635662;178635661;178635660	chr2:179500389;179500388;179500387
N2B	4823	14692;14693;14694	chr2:178635662;178635661;178635660	chr2:179500389;179500388;179500387
Novex-1	4948	15067;15068;15069	chr2:178635662;178635661;178635660	chr2:179500389;179500388;179500387
Novex-2	5015	15268;15269;15270	chr2:178635662;178635661;178635660	chr2:179500389;179500388;179500387
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-89
• Domain position: 13
• Structural Position: 24
• Q(SASA): 0.9431
• 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/N	rs1459382951	0.298	0.883	N	0.556	0.126	0.139678290688	gnomAD-2.1.1	4.38E-06	None	None	None	None	N	None	0	3.1E-05	None	0	0	None	0	None	0	0	0
K/N	rs1459382951	0.298	0.883	N	0.556	0.126	0.139678290688	gnomAD-4.0.0	1.13721E-05	None	None	None	None	N	None	0	1.66786E-04	None	0	0	None	0	0	0	0	0
K/R	rs1324858653	0.099	0.015	D	0.399	0.165	0.194818534648	gnomAD-4.0.0	1.62396E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91279E-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
K/A	0.7335	likely_pathogenic	0.7617	pathogenic	0.063	Stabilizing	0.74	D	0.595	neutral	None	None	None	None	N
K/C	0.9359	likely_pathogenic	0.9389	pathogenic	-0.011	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
K/D	0.9127	likely_pathogenic	0.9172	pathogenic	-0.018	Destabilizing	0.909	D	0.542	neutral	None	None	None	None	N
K/E	0.6028	likely_pathogenic	0.6133	pathogenic	-0.012	Destabilizing	0.682	D	0.597	neutral	N	0.520038641	None	None	N
K/F	0.9581	likely_pathogenic	0.9642	pathogenic	-0.124	Destabilizing	0.984	D	0.742	deleterious	None	None	None	None	N
K/G	0.5804	likely_pathogenic	0.6163	pathogenic	-0.142	Destabilizing	0.009	N	0.497	neutral	None	None	None	None	N
K/H	0.6711	likely_pathogenic	0.6697	pathogenic	-0.444	Destabilizing	0.987	D	0.515	neutral	None	None	None	None	N
K/I	0.9228	likely_pathogenic	0.9354	pathogenic	0.529	Stabilizing	0.953	D	0.774	deleterious	None	None	None	None	N
K/L	0.7307	likely_pathogenic	0.7849	pathogenic	0.529	Stabilizing	0.909	D	0.459	neutral	None	None	None	None	N
K/M	0.6518	likely_pathogenic	0.6832	pathogenic	0.314	Stabilizing	0.994	D	0.548	neutral	D	0.52714921	None	None	N
K/N	0.7839	likely_pathogenic	0.8087	pathogenic	0.37	Stabilizing	0.883	D	0.556	neutral	N	0.476154735	None	None	N
K/P	0.9746	likely_pathogenic	0.9741	pathogenic	0.401	Stabilizing	0.984	D	0.565	neutral	None	None	None	None	N
K/Q	0.4036	ambiguous	0.3975	ambiguous	0.192	Stabilizing	0.883	D	0.627	neutral	D	0.523599715	None	None	N
K/R	0.1323	likely_benign	0.1216	benign	0.025	Stabilizing	0.015	N	0.399	neutral	D	0.523403735	None	None	N
K/S	0.8083	likely_pathogenic	0.8241	pathogenic	-0.07	Destabilizing	0.74	D	0.589	neutral	None	None	None	None	N
K/T	0.6621	likely_pathogenic	0.698	pathogenic	0.079	Stabilizing	0.883	D	0.539	neutral	D	0.523403735	None	None	N
K/V	0.8656	likely_pathogenic	0.8818	pathogenic	0.401	Stabilizing	0.953	D	0.647	neutral	None	None	None	None	N
K/W	0.9643	likely_pathogenic	0.9633	pathogenic	-0.158	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
K/Y	0.9064	likely_pathogenic	0.9078	pathogenic	0.191	Stabilizing	0.984	D	0.669	prob.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.