Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000733208 | SCV000861244 | uncertain significance | not provided | 2018-05-29 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV002470965 | SCV002769036 | uncertain significance | Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis | 2020-06-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3A-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from serine to isoleucine (exon 10). (N) 0212 - Non-canonical splice variant without proven consequence on splicing (no functional evidence available). (P) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (19 heterozygotes, 0 homozygotes). (P) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (N) 0505 - Abnormal splicing is predicted by expert analyses and affected nucleotide is highly conserved. (P) 0600 - Variant is located in an annotated domain or motif (EPTP domain; NDBI, PDB). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0804 - Variant has previously been described as variant of uncertain significance (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1201 - Heterozygous variant detected in trans with a second (at least likely) pathogenic heterozygous variant in a recessive disease. (P) 1205 - Variant is maternally inherited. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |
| Labcorp Genetics |
RCV000733208 | SCV003293454 | pathogenic | not provided | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 585 of the TSPEAR protein (p.Ser585Ile). This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon. This variant is present in population databases (rs782716325, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features consistent with ectodermal dysplasia (PMID: 34042254; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 597169). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000733208 | SCV003842488 | uncertain significance | not provided | 2023-03-10 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: Jackson[CaseReport]2023, 34042254) |
| Duke University Health System Sequencing Clinic, |
RCV002470965 | SCV003919030 | uncertain significance | Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis | 2023-04-20 | criteria provided, single submitter | research |