Table 1.
Homozygous Variants Identified within the DFNB86 Interval
| Gene | Varianta | mRNA Changeb | Deduced Effect on Proteinb | Family | Mutation Type | Allele Frequency in EVSc | Allele Frequency in Control Chromosomes |
|---|---|---|---|---|---|---|---|
| CACNA1H | g.1257427G>A | c.3060G>A (NM_001005407.1) | p.Ala1020Ala (NP_001005407.1) | PKDF799 | synonymous | 3/12,229 | 2/174 |
| IGFALS | g.1841013C>T | c.1520G>A (NM_001146006.1) | p.Arg507His (NP_001139478.1) | DEM4476 | missense | 0/12,875 | -d |
| TBC1D24 | g.2546357G>T | c.208G>T (NM_001199107.1) | p.Asp70Tyr (NP_001186036.1) | PKDF799 | missense | 0/12,875 | 0/682 |
| TBC1D24 | g.2546357G>T | c.208G>T (NM_001199107.1) | p.Asp70Tyr (NP_001186036.1) | DEM4221 | missense | 0/12,875 | 0/682 |
| TBC1D24 | g.2547027G>C | c.878G>C (NM_001199107.1) | p.Arg293Pro (NP_001186036.1) | DEM4476 | missense | 0/12,875 | 0/634 |
| PRSS27 | g.2762774C>T | c.720G>A (NM_031948.3) | p.Ser240Ser (NP_114154.1) | PKDF799 | synonymous | 61/12,875 | 0/490 |
| PRSS27 | g.2762774C>T | c.720G>A (NM_031948.3) | p.Ser240Ser (NP_114154.1) | DEM4221 | synonymous | 61/12,875 | 0/490 |
| SRRM2 | g.2819161_2819163delTCT | c.7897_7899delTCT (NM_016333.3) | p.Ser2633del (NP_057417.3) | DEM4476 | in-frame deletione | 49/12,396 | 1/290 |
| THOC6 | g.3077605C>T | c.973C>T (NM_024339.3) | p.Arg280Trpf (NP_077315.2) | DEM4221 | missense | 0/12,875 | 0/148 |
a
Coordinates are based on the hg19 human reference sequence (UCSC Genome Browser).
b
RefSeq accession numbers are shown in parentheses.
c
NHLBI Exome Sequencing Project (ESP) Exome Variant Server.
d
Arg507 is not conserved in mouse, rat, or dog. The substitution of His for Arg507 is predicted to be neutral by MutationTaster, PolyPhen-2, SIFT, LRT, and MutationAssessor.
e
This deletion of three nucleotides is one of several similar indels previously reported in the EVS as common SNPs resulting in deletion or insertion of one or more serine residues in a stretch of 42 consecutive serines.
f
Does not cosegregate with deafness in family DEM4221.