Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001811170 | SCV002048354 | likely pathogenic | not provided | 2021-04-09 | criteria provided, single submitter | clinical testing | The Hb Sallanches variant (HBA2: c.314G>A; p.Cys105Tyr, also known as Cys104Tyr when numbered from the mature protein, rs41417548) is reported in the literature in the homozygous or compound heterozygous state in multiple individuals with Hb H disease (Hb Var and references therein, Sharma 2020). Functional analyses show the variant protein is unstable and display a defect in binding with alpha-hemoglobin stabilizing protein (Sharma 2020, Wajcman 2011). This variant is reported in ClinVar (Variation ID: 15656). This variant is found in the South Asian population with an allele frequency of 0.017% (5/30278 alleles) in the Genome Aggregation Database. The cysteine at codon 105 is moderately conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.678). Based on available information, this variant is considered to be likely pathogenic. References: Hb Var for Hb Sallanches: https://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=167&.cgifields=histD Sharma P et al. HbH disease due to compound heterozygosity for hemoglobins Zürich-Albisrieden and Sallanches. Pediatr Blood Cancer. 2020 Apr;67(4):e28161. PMID: 31930682. Wajcman H et al. a-Hemoglobin stabilizing protein: a modulating factor in thalassemias? Hemoglobin. 2011;35(5-6):463-8. PMID: 21950764. |
| 3billion | RCV002051787 | SCV002318546 | pathogenic | alpha Thalassemia | 2022-03-22 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with [GeneName] related disorder (ClinVar ID: VCV000015656, PMID:8555062). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 10722113). A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000804215, PMID:23181747). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.678>=0.6). A missense variant is a common mechanism . Itis observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0000202). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Ce |
RCV001811170 | SCV004131653 | pathogenic | not provided | 2022-08-01 | criteria provided, single submitter | clinical testing | HBA2: PM3:Very Strong, PM2, PP1:Moderate, PS3:Supporting |
| Breakthrough Genomics, |
RCV004595884 | SCV005088889 | pathogenic | Hemoglobin H disease | 2023-07-13 | criteria provided, single submitter | clinical testing | This variant (also known as Hb Sallanches variant; Cys104Tyr) has been previously reported multiple individuals with Hemoglobin H disease in homozygous state [PMID: 11186268, 8555062, 10722113, 20113287]. Functional analyses showed the variant protein is unstable and display a defect in binding with alpha-hemoglobin stabilizing protein [31930682, 21950764]. |
| OMIM | RCV000016942 | SCV000037214 | other | HEMOGLOBIN SALLANCHES | 2013-03-28 | no assertion criteria provided | literature only | |
| OMIM | RCV000022606 | SCV000043895 | pathogenic | Hemoglobin H disease, nondeletional | 2000-02-01 | no assertion criteria provided | literature only |